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Bioinformatic Analysis of Oncogenes and Tumour Suppressor Genes in Selected Cancers

Info: 119015 words (476 pages) Dissertation
Published: 11th Dec 2019

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Tags: MedicalCancer

Bioinformatic Analysis of Oncogenes and Tumour Suppressor Genes in Selected Cancers for their Diagnostic and Prognostic Value

Abstract

Cancers are a diverse range of diseases characterised by gene mutations that result in uncontrolled cell proliferation and lead to the generation of tumours. Genes that are often mutated in cancer are known as oncogenes and these mutant genes can be used as biomarkers to reveal the pathways behind cancer formation and shed light on potential treatment options and expected progression. In this study BRAF is the oncogene biomarker under investigation. Clinical BRAF samples were compared to a clinical reference samples using multiple sequence alignment of amino acid sequences. This allowed the detection of the most commonly mutated amino acids in the clinical data set as well as the nature of these mutations and their deviation from the reference sequence. Amino acid 600 was revealed to be the most commonly mutated amino acid in the data set, accounting for 7 out of the 10 mutations present in the clinical data set. In addition to multiple sequence alignment, models of mutant and wild type proteins were compared to identify structural differences between them and identify the cause of the oncogenic activity. This revealed that the mutations on amino acid 600 disrupts the structure of the activation loop of the kinase binding domain. This renders B-Raf unable to retain an inactive state and promotes cell proliferation. Primers were also designed in order to evaluate to ability of PCR based amplification to detect these mutations to amino acid 600. These primers gave a suitable PCR result, with amino acid 600 falling within the range of the amplification segment. COSMIC (Catalogue of Somatic Mutations in Cancer) was also used to investigated the specific types of cancer associated with certain mutations as well as to identify other mutation hotspots and define their structural alterations. Published literature was also investigated to research the mechanisms of action in pathways associated with BRAF and the impacts of targeted anti-BRAF therapies over long term cancer treatment.

Acknowledgments

I would like to offer my sincerest gratitude to my project supervisor Dr. Ralph Rapley for his support, encouragement and guidance throughout this project, without which this project would have been impossible to complete.

Contents

Acknowledgments…………………………………………

List of Figures……………………………………………

1. Introduction……………………………………………

1.1 General aspects of oncology……………………………….

1.2 Risk factors, carcinogens, formation genetic and sporadic tumours………

1.3 Genes involved in early tumour formation………………………

1.4 Oncogenes and Tumour Suppressors…………………………

1.5 Aims and Objectives……………………………………

2. Methods………………………………………………

3. Results………………………………………………

3.1 Details on Gene of Study…………………………………

3.2 Multiple Sequence Alignment………………………………

3.3 Protein Models

3.4 In-Silico PCR…………………………………………

4. Discussion…………………………………………….

4.1 Identification of gene mutations (Biomarkers) as an aid to diagnosis………

4.2 Identification of gene mutations (Biomarkers) as an aid to prognosis and treatment…….

4.4 Bioinformatic Tools…………………………………….

4.5 Future of diagnostics……………………………………

References……………………………………………..

List of Figures

Table 1.2: Table of oncogenes

Table 1.1: Table of tumour suppressor genes.

Figure 2.1: OMIM database page for BRAF gene

Figure 2.2: NCBI database page for BRAF gene.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.7: COSMIC gene view of BRAF cDNA sequence

Figure 2.8: BRAF mutation hotspot in COSMIC

Figure 2.9: Close up view of V600 peak

Figure 2.10: V600E BRAF mutation COSMIC page.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder

Figure 2.13: Clustal Omega multiple sequence alignment.

Figure 2.14: BRAF transcript on the ENSEMBL database

Figure 2.15: Protein summary selection on ENSEMBL

Figure 2.16: ENSEMBL graphical display of protein domains.

Figure 2.17: SWISS-MODEL entry.

Figure 2.18: SWISS-MODEL results.

Figure 2.19: NCBI Primer BLAST

Figure 2.20: UCSC In-Silico PCR.

Figure 3.1: Results of multiple sequence alignment.

Figure 3.2: Protein models V600

Figure 3.3: Protein models G469R mutations.

Figure 3.4: Results of primer BLAST

Figure 3.5: Results of UCSC In-Silico PCR.9

Figure 3.6:Map of UCSC In-Silico PCR product.

1. Introduction

Oncogenes and tumour suppressor genes are genes that are commonly mutated in a wide range of cancers. In some cancer types, mutations to key oncogenes and/or tumour suppressor genes are found in up to 80% of cancer samples. As such these genes are key targets of interest, as understanding the pathways that caused the development of cancer will allow a more efficient targeted treatment. In addition, expression of these mutated genes may also allow more rapid and less invasive diagnosis of cancer type and malignancy.

Cancers are a group of diseases characterised by their uncontrolled proliferation which leads to the eventual generation of cancerous tumours. There are over 200 different types of cancers and different cancers can be comprised of completely different types of cells making cancers a highly variable and hard to treat group of diseases. In addition to their rapid proliferation, cancers can also be invasive, metastasising to nearby tissues and can also be carried in the bloodstream or lymphatic system to other parts of the body, where new secondary tumours may form. Cancers are caused by mutations in DNA that lead to deregulation of the cell cycle and cell growth, genes commonly mutated in cancers are known as oncogenes, while genes that protect the body against cancer development are called tumour suppressor genes.

While some mutations are prominently linked to certain cancers, most known biomarkers are not effective targets for cancer diagnosis, as presence of a certain biomarker is not necessarily indicative of cancer presence. Likewise, lack of biomarker presence does not necessarily indicate the patient to cancer free. Biomarkers do however play an invaluable role in modern cancer prognosis, knowledge of the mutations present in cancers is a useful tool in deciding the treatment path for patients. For example, the overexpression of oestrogen receptors (ERs) is present in over 50% of breast cancers, patients with mutations leading to enhanced ER activity are

far more responsive to selective oestrogen receptor modulator (SERM) treatment pathways, such as tamoxifen. In addition to predicting the response to treatment types, knowing the mutations present in cancer also allows a more accurate prediction of a cancers malignancy and progression path.

1.1 General aspects of oncology

Oncology is a branch of medicine that focuses on cancer diagnosis and treatment. Diagnosis of cancer requires different methods depending on the type of cancer and its location, the most consistently accurate method of diagnosis for almost all cancers is a biopsy of a suspected sample. However, the position of cancer can impact the ease with which samples for biopsy can be obtained. For example, in the case of basal cell carcinoma, excision of tissue for analysis is far easier and less invasive than obtaining a biopsy of prostate cancer cells. As such new, potentially non-invasive methods for diagnosing cancers and evaluating their malignancy is a high priority for oncologists, as early diagnosis of cancer is one of the most important factors in being treated successfully.

The development and progression of bioinformatic techniques, combined with their ease of access has dramatically affected the field of oncology. Bioinformatics combines computational techniques with large online databases containing data on genes and their sequence, function and expression. These databases allow researchers to retrieve data on genes for wild-scale comparison such as multiple sequence alignments. Techniques such as these can be combined with catalogues of clinically significant mutation data to investigate the prominence of specific mutations in specific cancer types. Bioinformatic analysis of the human BRAF gene in cancer is the focus of this study.

1.2 Risk factors, carcinogens, formation genetic and sporadic tumours

Cancer is one of the most prominent human diseases with around 12.7 million new cancer cases reported worldwide in 2008 and 7.6 million cancer deaths (Jemal et al., 2011). While many risk factors for cancer development have been discovered, there are still millions of cases of cancer a year where the reason for cancer development is not known. There are also many factors that are suspected, but not proven, to be linked to cancer development. For example, exposure to the pesticide Malathion has been suggested to increase the risk of developing prostate cancer (Koutros et al., 2013), but more investigation is required to confidently define it as a risk factor.

The most common and avoidable risk factor for cancer development is smoking, with an estimated 80% of lung cancer deaths being attributed to smoking (Peto, 2000). As such cancer patients are always advised to stop smoking due to the large number of toxic chemicals and carcinogens present in cigarette smoke. A carcinogen is something that can be directly implicated in causing cancer. While the most commonly mentioned carcinogens are chemicals such as Benzo[a]pyrene, which is found in tobacco smoke. Other substances and even organisms can also cause cancer in humans, radiation can cause cancer development via DNA damage, and some microbial agents produced by fungi also have carcinogenic properties. Viruses can also cause the development of cancer, Hepatitis B and HPV have both been found to be carcinogenic, increasing the likelihood of liver and cervical/mouth/throat cancers respectively.

A multitude of hereditary genetic disorders can also increase the chance of cancer development. One of the most common and well researched of these cancer syndromes is Familial adenomatous polyposis (FAP), in which many benign adenomas form in the colon due to a mutated APC gene leading to the accumulation and upregulation of β-catenin and its associated pathways controlling cell proliferation and migration-. The benign adenomas have a high risk of developing into cancers due to the lack of β-catenin regulation (MacDonald, Tamai, & He, 2009). Another cancer syndrome is the mutations of BRCA1 and BRCA2 known as Hereditary breast and ovarian cancer (HBOC) which increases the risk of breast and ovarian cancer in women and prostate cancer in men. BRCA1 and BRCA2 are both genes whose function is based in DNA maintenance and repair, so mutations in these genes inhibit the body’s natural failsafe against DNA damage and present a greater opportunity for DNA damage to progress to cancer.

Sporadic cancers are far more common than those arising from hereditary conditions and comprise the majority of all cancers. These sporadic tumours form when DNA becomes damaged or mutated, altering or inhibiting the functionality of key proteins, usually those relating to DNA repair. However, most cancers do not contain mutations directly to the genes coding for DNA repair proteins but arise due to due epigenetic silencing of DNA repair gene expression.

1.3 Genes involved in early tumour formation

Tumours can arise from a wide variety of different human tissues, given such a wide variety of tumour types it’s no surprise that the genes involved in the formation of tumours can vary hugely. Many oncogenes and tumour suppressor genes can be responsible for early tumour growth. Tumour suppressor genes widely follow the “two-hit hypothesis” requiring both alleles of the gene to be mutated to express the effect of the mutation, while oncogenes mostly require only one mutated allele.

The Ras family of proteins are highly implicated in early tumour formation, being frequently mutated in many human cancers, as such they are a well-researched family of oncogenes. There are 3 genes encoding for Ras family proteins HRAS, NRAS and KRAS, and the Ras protein isoforms are GTPases that act as switches, when GTP is bound to the GTPases they are in the active state and activate the signal transduction pathway associated with the GTPase. To inactivate the pathway the bound GTP is irreversibly hydrolysed by GTPase to GDP which renders the signal transduction inactive. In order for the GTPase to be made active again via the action of Guanine nucleotide exchange factors (GEFs) which displace the GDP and allow a new GTP to bind and activate the signalling pathway. Point mutations to any of three Ras isoforms, H-Ras, N-Ras and K-Ras are largely associated with hyperproliferative disorders and are typically associated with a single point mutation at codons 12, 13 or 61 (Prior, Lewis, & Mattos, 2012). In some studies K-Ras mutations have been found in up 90% of analysed pancreatic cancer samples, typically K-Ras mutations are localised to codon 12, with around 80% of mutations at this location.

Many genes can be associated with the early development of tumours, but the most consistently mutated genes in cancers are associated with cell cycle regulation (Giacinti, & Giordano, 2006). Loss of cell cycle regulatory abilities is a key step in providing a favourable environment for deregulated hyperproliferation of poorly-differentiated cells characteristic of malignant tumour growth. Promotion of cell survival and repression of apoptotic pathways through mutations to tumour suppressor genes are also potent promoters of tumour formation. This highlights many genes associated with the cell cycle as potential biomarkers for use in the detection of early stage tumours and even precancerous growths. Greater understanding of these control pathways may also reveal new targets for cancer treatments and methods to counteract the effects of specific mutations.

1.4 Oncogenes and Tumour Suppressors

In addition to mutations, oncogenes can also be activated via amplification, where cell signalling and microenvironment lead to the production of extra gene copies and the subsequent increased expression associated causes oncogene activation. The consequences of mutant oncogenes or tumour suppressor genes can be broadly categorised based on the “Hallmarks of Cancer” laid out by Douglas Hanahan and Robert Weinberg in 2000 in their article in Cell. These hallmarks were listed as: Self-sufficiency in growth signals, Insensitivity to anti-growth signals, Evading apoptosis, Limitless replicative potential, Sustained angiogenesis and Tissue invasion and metastasis (Hanahan, & Weinberg, 2000). The majority of single oncogenes and tumour suppressor genes contribute to the establishments of up to two of these hallmarks.

Tumour Suppressor Gene De-activation of Tumour Suppressor Gene Consequence of Mutant Protein
PI3K Point Mutation Apoptosis Evasion
LKB1 Point Mutation Deregulated Cell Growth, Sustained Angiogenesis
PTEN Point Mutation, Deletion Apoptosis Evasion
p15 Point Mutation Deregulated Cell Growth.
p16 Point Mutation Deregulated Cell Growth.
Rb Point Mutation Deregulated Cell Growth.
BRCA1 Point Mutation Deregulated Cell Growth, Resistance to Anti-Growth Signalling
p53 Point Mutation, Deletion Apoptosis Evasion, Resistance to Anti-Growth Signalling
Ptch Point Mutation Deregulated Cell Growth, Apoptosis Evasion
Integrin Deletion Invasiveness/Metastasising
NF1 Point Mutation, Deletion Deregulated Cell Growth
NF2 Point Mutation, Deletion Deregulated Cell Growth, Invasiveness/Metastasising
TGFβR Point Mutation Resistance to Anti-Growth Signalling
APC Point Mutation Deregulation Cell Growth
Axin Point Mutation Deregulated Cell Growth
α-catenin Point Mutation Invasiveness/Metastasising
E-cadherin Point Mutation Deregulated Cell Growth, Resistance to Anti-Growth Signalling, Invasiveness/Metastasising

Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.Table 1.1: Table showing a number of tumour suppressor genes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Table 1.2: Table showing a number of oncogenes and the mutations or modifications that occur in them, as well as the cancer hallmark their modifications contribute to. The oncogene of focus in this report is BRAF.

Oncogene Activation of Oncogene Consequence of Mutant Protein
Akt Point Mutation Increased expression, Apoptosis Evasion
Cdk-2 Amplification Deregulated Cell Growth
Cyclin E Amplification Deregulated Cell Growth
HPV-E7 Viral Infection Deregulated Cell Growth
Mdm2 Amplification Apoptosis Evasion
Fas Point Mutation Apoptosis Evasion
Gli Amplification, Translocation Deregulated Cell Growth, Apoptosis Evasion
Hedgehog Point Mutation Deregulated Cell Growth, Apoptosis Evasion
Smo Point Mutation Deregulated Cell Growth, Apoptosis Evasion
Notch Translocation Apoptosis Evasion
B-Raf Point Mutation, Amplification Deregulated Cell Growth
Ras Point Mutation Deregulated Cell Growth
Myc Point Mutation, Amplification Deregulated Cell Growth
β-catenin Point mutation Deregulated Cell Growth
HOXs Translocation, Point Mutation Deregulated Cell Growth

It is notable that tumour suppressor genes are not susceptible to amplification modifications, whereas they are prominent activators of oncogenes, in addition, tumour suppressor genes seem notably more susceptible to deletion mutations. Given the antioncogenic nature of tumour suppressor genes, it is likely that most deletion and point mutations are characteristic of loss of protective function associated with tumour suppressor genes. By comparison, oncogenes are almost always activated by an increase in function as a result of amplification or missense mutations that result in the disruption of important protein binding sites.

1.5 Aims and Objectives

The aim of this report is to use bioinformatic techniques and published research to investigate the oncogene BRAF and its mutations. This is done in order to evaluate the effectiveness of BRAF as a biomarker for the diagnosis and prognosis of specific cancer types.

2. Methods

The first step was establishing the gene of interest and characterising basic features such as cytogenic location and expression locations. OMIM (Online Mendelian Inheritance in Man) was the first database consulted. OMIM gave the cytogenic locations of the gene, as well as links to NCBI genome maps and gene pages, as shown in Figure: 2.1. The NCBI database entry for BRAF showed the number of exons in the gene as well as giving a link to download the sequence in the FASTA file format shown in Figures 2.2, 2.3 and 2.4.

The next step was to use the COSMIC (Catalogue of Somatic Mutations in Cancer) database to identify to retrieve the cDNA sequence of BRAF as well as analyse the locations of mutation hotspots and the specific cDNA sequence alterations responsible for mutation shown in Figure 2.5 and 2.6. The COSMIC gene viewer was used to locate mutations and characterise their alterations shown in Figures 2.7, 2.8 and 2.9. Each mutation also had database entries detailing tissue distribution and clinical samples shown in Figure 2.10. Clinical mutant BRAF samples were also obtained from the NHS genomics clinical data set shown in Figure 2.11. These samples were translated into amino acid sequences using ORF finder and these amino acid sequences used in Clustal Omega to perform sequence alignment to identify deviations from the reference sequence as shown in Figures 2.12 and 2.13. After performing the sequence alignment ENSEMBL genome browser was used to determine the domains present in B-Raf transcripts shown in Figures 2.14, 2.15 and 2.16. SWISS-MODEL was then used to create models of proteins of interest in order to compare the structural differences between mutant and wild-type proteins, amino acid sequences of B-Raf proteins of interest were inputted to create the models shown in Figures 2.17 and 2.18. Finally, primers were designed using NCBI Primer-BLAST, the forward and reverse primers gave were inputted into UCSC In-Silico PCR program to determine suitability for PCR-based mutation detection shown in Figures 2.19 and 2.20.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.

Figure 2.3: NCBI genome viewer link to BRAF FASTA fileFigure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.1: OMIM database page for BRAF gene, showing cytogenic location and link to NCBI genome map.Figure 2.2: NCBI database page for BRAF gene showing the number of exons.

Figure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequenceFigure 2.3: NCBI genome viewer link to BRAF FASTA file

Figure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

Figure 2.6: BRAF cDNA sequence from COSMICFigure 2.4: NCBI FASTA view and download link for BRAF sequence

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Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence link

Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnifiedFigure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

Figure 2.5: COSMIC BRAF gene overview and cDNA sequence linkFigure 2.6: BRAF cDNA sequence from COSMIC

C:UsersAndreasAppDataLocalMicrosoftWindowsINetCacheContent.WordCOSMICV600Ezoom.png

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

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Figure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspot. Was then converted to cDNA sequence.

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutationFigure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.7: COSMIC gene view of BRAF amino sequence, a large peak at amino acid 600 indicated a very common mutation hotspotFigure 2.8: BRAF mutation hotspot in COSMIC gene view was magnified

Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.Figure 2.9: Close up view of V600 peak, showing cDNA substitution of T>A giving rise to a V>E amino acid substitution- V600E mutation

Figure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

Figure 2.11: NHS Genomics anonymised clinical samplesFigure 2.10: V600E BRAF mutation COSMIC page gave tabs to investigate the tissue distribution and view clinical sample data.

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Figure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequencesFigure 2.11: NHS Genomics anonymised clinical samples

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Figure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selectedFigure 2.12: ORF finder was used to translate clinical sample nucleotide sequences and full BRAF cDNA to amino acid sequences

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

.

Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

.

Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

.

Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

.

Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

.

Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

.

Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

.

Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

.

Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

.

Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

.

Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

Figure 2.13: Amino acid sequences of clinical samples and reference sequence, as well as complete BRAF wild type sequence were entered into Clustal Omega to perform multiple sequence alignment.Figure 2.14: The first BRAF transcript on the ENSEMBL database was selected

C:UsersAndreasAppDataLocalMicrosoftWindowsINetCacheContent.WordENSEMBLE DOMAINS.JPG

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

.

Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

.

Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

.

Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLE

Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

Figure 2.15: After selecting the transcript, protein summary was selected on the left-hand menu on ENSEMBLEFigure 2.16: The protein summary on ENSEMBLE showed a graphical display of protein domains.

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Figure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

.

Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

.

Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

.

Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

.

Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

.

Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

.

Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

.

Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

.

Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

.

Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequencesFigure 2.17: Amino acid sequences of proteins were entered into SWISS-MODEL to model proteins for structural comparisons.

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C:UsersAndreasAppDataLocalMicrosoftWindowsINetCacheContent.WordPRIMERBLAST.JPGC:UsersAndreasAppDataLocalMicrosoftWindowsINetCacheContent.WordSwissprot.png

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.

Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode GenesFigure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

Figure 2.18: SWISS-MODEL was used to produce models of mutant and wild type proteins to allow analysis of conformational differences associated with mutations.Figure 2.19: NCBI Primer BLAST was used to design primers for PCR amplification of V600 region of BRAF sequences

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Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).Figure 2.20: The forward and reverse primers produced by the Primer BLAST were entered into the UCSC In-Silico PCR web-app (http://genome.ucsc.edu) and In-Silico PCR was run targeting Gencode Genes from the December 2013 assembly.

3. Results

3.1 Details on Gene of Study

The gene investigated in this report was the B-Raf proto-oncogene, serine/threonine kinase (BRAF) gene, located on chromosome 7q34 and contains 21 exons, the transcribed mRNA of BRAF contains` 2478 bp. BRAF is a Raf kinase family member, these proteins act as growth signal receptors and are key signal transducers in the mitogen-activated protein kinase (MAPK) cascade. This signalling cascade uses a number of proteins to transmit a signal from the surface of the cell to the DNA in the nucleus. The MAPK/ERK proteins are phosphorylated to activate them and then phosphorylate the next protein in the signalling cascade to pass on the signal. The MAPK/ERK pathway regulates the expression and activity of a number of transcription factors such as c-myc and C-Fos and as such, plays a significant role in the expression of genes key to cell cycle control. B-Raf is a 766-amino acid protein with the characteristic 3 conserved domains of all the Raf kinase proteins. The three domains are: Raf-like Ras-binding domain (RBD), Protein kinase C-like phorbol ester/diacylglycerol-binding domain (C1 domain) and protein kinase domain. B-Raf is present in all tissue types, however, mRNA expression is significantly higher in tissues with high rates of cell division, such as testis tissue.

3.2 Multiple Sequence Alignment

C:UsersAndreasAppDataLocalMicrosoftWindowsINetCacheContent.WordSequence Alignment.jpgClinical sequences from NHS regional genomics data set were obtained and their amino acid sequences used to produce a multiple sequence alignment, shown in Figure 3.1.

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

Figure 3.1: Results of multiple sequence alignment of amino acid sequences belonging to clinical sequences in order to compare protein structure between mutant and wild type (reference sample).

In addition to the 5 clinical samples with V600 mutations, there were also two samples with mutations present on the 597th amino acid residue, which is usually a leucine (L) residue. These L597 mutations are substitutions with leucine being replaced with a glutamine (Q) and arginine (R) respectively in the clinical samples L597Q and L597R. In addition to the clinical samples from the Regional Genetics NHS Trust data set, clinical BRAF mutations were also investigated using COSMIC. While V600 mutations are by far the most common mutations in BRAF there are numerous other smaller mutation hotspots along its coding sequence. One other mutation in BRAF is G469 mutation, caused by a substitution of a G to an A at the 1405th DNA base pair, giving rise a G to R missense amino acid sequence mutation on the 469th residue, in the highly conserved P-loop of the protein kinase domain. While clinical samples with this mutation present are limited compared to samples with V600 mutations, the majority of samples present are malignant melanomas of the skin or non-specified tissue. In addition to sequence alignments, models of mutant and wild type proteins were constructed in order to analyse structural and conformational differences between the proteins.

3.3 Protein Models

Models of the clinical V600E mutant and reference samples were created using SWISS-MODEL and used to identify conformational differences. Mutations to V600 result in disruption of the structure of the activation loop which associates with the P-loop of B-Raf to render it inactive. Another B-Raf protein with a G469R mutation was also modelled and compared to a wild type B-Raf model, this mutation results in structural disruption to the P-loop, interfering with activation loop binding

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.2: Protein models of amino acid sequences from clinical samples in a V600E mutant (Left) and the clinical reference sequence (Right) B-Raf. Mutation is associated with loss of hydrophobic interactions between activation loop and P-loop which is essential for allowing B-Raf to maintain an inactive state when not phosphorylated. Loss of interaction between these loops results in aberrant activation of B-Raf.

Figure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

Figure 3.5: Results of UCSC In-Silico PCRFigure 3.3: Protein models of B-Raf wild type (Left) and B-Raf with G469R mutations (Right). Mutation takes place in highly conserved GXGXXG motif of the P-loop in the kinase domain. Association of the P-loop to the activation loop is required to maintain and inactive protein state.

3.4 In-Silico PCR

The NCBI primer BLAST tool was used to create a set of primers suitable for use in the detection of V600 mutation in BRAF.  After the forward and reverse primers were generated they were re-entered intro the primer BLAST tool in order to determine their specificity to the sequence on the target protein. The results of this BLAST are shown in figure 3.4 and confirmed the specificity of the primers. The UCSC In-Silico PCR tool was used to examine the viability of the primers, and yielded 3 potential sequences on BRAF that could be amplified by these primers. The first of these amplified a 172bp sequence from 1765bp-1934bp on the BRAF gene, shown in Figure 3.5 and 3.6.

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Figure 3.4: Results of the primer-BLAST used to confirm the specificity of the primer pair to BRAF. All of the results amplify an appropriate length sequence from BRAF. However, this fails to confirm whether the primers will amplify across the target bases (base 1799 for V600 mutations).

Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

Figure 3.6: Figure 3.5: Results of UCSC In-Silico PCR. The first result gives the optimal products including the target bases. Details on the primers and their melting points are also shown.

C:UsersAndreasAppDataLocalMicrosoftWindowsINetCacheContent.Wordin silico.png4. Discussion

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

 

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

Figure 3.6: Gene map showing the bases amplified by In-Silico PCR. The V600 mutation falls within this amplicon.

4.1 Identification of biomarkers as an aid to diagnosis.

Identification of BRAF mutations in key cancer types is vitally important to providing an accurate prognosis and predicting the effectiveness of treatment options. Unfortunately, BRAF is not an effective biomarker for cancer diagnosis, this is because all cancers associated with BRAF mutations can occur via numerous BRAF-independent pathways. In addition, the most effective method of cancer diagnosis is performing a biopsy on a suspected cancer sample, this would give a more accurate diagnosis of cancer than performing genetic screening on the sample to identify BRAF as an oncogenic agent. However, BRAF biomarkers can potentially shed light on the origin of a secondary tumour and its progression (Davies et al., 2002).

4.2 Identification of biomarkers as an aid to prognosis and treatment.

Identification of BRAF mutations in key cancer types is, however vitally important to providing an accurate prognosis and predicting the effectiveness of treatment options. Establishing whether BRAF mutations are present in a cancer- specifically melanoma, is key to prescribing optimal treatment. BRAF mutations in melanomas are associated with greatly increased sensitivity to B-Rafinhibitor based treatment such as vemurafenib (Zelboraf) or dabrafenib (Tafinlar). In V600E positive melanomas, Vemurafenib triggers apoptosis of cancer cells via interruption of the B-Raf/MEK step of the MAPK/ERK pathway and is also a functional treatment for V600K mutations. However, like most cancer therapies, over time cancers begin to develop resistance to treatment, in the case of Vemurafenib, one method of resistance gain is via the upregulation of receptor tyrosine kinase-based survival methods and upregulation of N-Ras MAPK activation to promote circumvention of targeted B-Raf inhibition (Nazarian et al., 2010). Dabrafenibis another common BRAF inhibitor, like Vemurafenib it is associated with increased progression-free survival for patients, however, resistance to Dabrafenibtreatment begins to result in disease progression after 6-7 months (Flaherty et al., 2012).  Cancers with mutations other than V600 are rarer and less well understood, and the effects of B-Raf inhibitors on such cancers are unclear and likely mutation specific.

In addition to mutations that affect the protein kinase domain of B-Raf there are also rarer mutations that fall within the C1 and RBD domains of B-Raf. A substitution on base pair 769 from C to A gives rise to missense substitution from Q to K on amino acid 257 in the C1 domain. Clinical samples of this mutation are limited, but it has been detected in prostate cancer samples (Taylor et al., 2010). Clinical samples with mutations in the RBD domains are similarly rare, a C to T substitution on base pair 575 gives rise to a P to L missense substitution from P to L on the 192nd amino acid residue- this domain is essential to maintain control over kinase domain inhibition. Clinically significant BRAF mutations are always associated with upregulated MAPK/ERT pathway activity as the primary driving mechanism of cancer development.

Mutations other than V600 in melanoma are associated with increased patient age and cancer aggressiveness, as well as decreased effectiveness of B-Raf inhibitor drugs as treatment (Kim et al., 2014). This may be linked to the fact that melanomas with B-Raf mutations that are not on V600 are more likely to be accompanied by N-Ras mutations, which are associated with B-Raf inhibitor resistance in V600E mutant samples. It is necessary to achieve complete inhibition of MAPK/ERK pathway in order induce apoptosis in cancerous cells, therefore circumvention of B-Raf inhibitorresistance pathways is required for effective therapy. B-Raf inhibitor resistance has been successfully attenuated via the combination of anti-B-Raf dabrafenib and anti-MEK trametinib to achieve complete MAPK/ERK pathway inhibition and promote progression-free survival and cancer shrinkage (Gowrishankar, S., & Rizos, 2013).

In addition to its function as an oncogene, BRAF and the associated MAPK/ERK pathway also play a key role in embryo development and cell fate pathway. Due to this, hereditary BRAF mutations are associated with a number of developmental diseases such as cardiofaciocutaneous syndrome and giant congenital melanocytic nevus (Salgado et al., 2015). Cardiofaciocutaneous syndrome is associated with at least 49 different BRAF mutations, and BRAF mutations are the most common cause of the disease with 75% of cases caused by mutated BRAF (Ades, Sillence, & Rogers, 1992). Most mutations occur in the Ras-GTP binding region coding sequence, and the majority of BRAF disorders are the result of a disruption of Ras-GTP binding, which is usually required for BRAF activation. These mutations result in aberrant activation of B-Raf and the usually tightly regulated MAPK/ERK cascade, which culminates in the upregulation of cell proliferation and disruption cell differentiation pathways.

4.3 NHS clinical data set samples

Most of the clinical sequences in the alignment shown in Figure: 3.1 display mutations in the most common mutation hotspot in BRAF, the 600th amino acid residue in the protein, within the activation segment of the kinase domain. The clinical reference wild-type sequence shows that ordinarily, the 600th residue is valine (V). Hence mutations to this gene are known as V600 mutations and there 4 different V600 mutations in the clinical samples; V600E, V600M, V600K, V600G, each representing a substitution of the valine at the 600th position with; glutamic acid (E), methionine (M), lysine (K) and glycine (G) respectively. While BRAF mutations have been associated with the development of a number of cancers, they are most common in melanomas, present in 37–50% (COSMIC)​ of melanoma samples. Of all the V600 mutations, V600E is by far the most common mutation in melanoma, accounting for 80-90% (COSMIC) of all melanoma cases with BRAF mutations.

The L597 mutations in the alignment in Figure: 3.1 also fall in the kinase domain of the protein and as such are associated with upregulated kinase activity like V600 mutations, however, these mutations are not strongly associated with any particular cancer types. Perhaps this is partially due to the rarity of the mutation, being present in less than 1% of BRAF mutant melanomas. One of the clinical samples; P345wt, shows no mutations in the sequence alignment, suggesting that the patient had no BRAF mutation, however this does not mean that the patient was free of melanoma or other cancers. As such, further investigation may lead to uses for this gene in the differential diagnosis of malignant melanoma of the skin, but more samples will be required to elucidate a significant association between the mutation and a specific cancer type.

4.4 BRAF biomarker in Colorectal cancer

Colorectal cancer (CRC) is another cancer with which BRAF mutations are associated. The presence of mutant BRAF in CRCis indicative of reduced effectiveness of anti-BRAF therapies (Yuan et al., 2013), however, the response rate to anti-BRAF therapies varies greatly between CRC and melanoma. It is thought that anti-BRAF resistance is the result of complex interactions in the MAPK/ERK pathway that allow the circumvention of B-Raf inhibition via increased N-Ras activation. In melanoma, anti-BRAF resistance occurs as a result of activity from other MAPK/ERK cascade proteins such as MEK-1 MEK-2 which allows the circumvention of B-Raf-mediated pathways, rendering inhibitors of BRAF less effective as a treatment method (Barras, 2015).

4.5 Bioinformatic Tools

Online databases such as COSMIC and ENSEMBL along with tools such as CLUSTAL-OMEGA and NCBI-BLAST allow low cost high speed access to large amounts of information and processing tools. CLUSTAL can be used to perform sequence alignments between amino acid and nucleotide sequences, allowing deviations between gene or protein sequences to be easily identified and localised. This allows the rapid comparison of protein structures in clinical samples in order to determine the type and presence of mutant proteins and allows the selection of ideal targeted treatments. NCBI-BLAST is an essential tool which can be used to search for proteins or genes using parts of their amino acid or nucleotide sequence using sequence alignment to determine the most similar sequences. This allows functionally similar genes and homologs between species to be located and the compilation of this data thereby can serve to shed light on genes whose functions are unknown by rapidly identifying structurally similar proteins.

SWISS-MODEL was used to create protein models for structural comparison between mutant and wild-type proteins. Such protein modelling tools are useful for determining how a mutation effects the tertiary structure of a protein and interactions between key functional domains, this can in turn shed light on the mechanisms through which mutant phenotypes are expressed. In-Silico PCR is another valuable bioinformatic tool, the ability to conduct a “dry” PCR allows primer pairs to be optimised for selectiveness and efficiency, ensuring that the binder will bind specifically to the correct target points and reduce the amplification of non-target material. In addition to allowing greater primer optimisation In-Silico PCR is also highly useful for initial primer design to ensure identity with target sequences, reveal the primer melting points, and allow the size and conformation of the amplified product to be predicted (Kalendara, Lee, & Schulman, 2011).

4.6 Future of diagnostics

High throughput “next generation” sequencing methods are dramatically changing the way DNA and RNA sequencing is performed, these methods are far cheaper and faster than the most commonly used Sanger sequencing.  These NGS methods have made it possible to sequence an entire human genome in a single day. The human genome project, which began in 1990 was the first time the human genome was sequenced and it took over a decade to complete the project and collate the data (Behjati, & Tarpey, 2013). With the advent of NGS techniques, further projects have been announced that seek to sequence the genomes of a large number of humans in order to ultimately attempt to construct a comprehensive database of human genes. One such project is the 100k genomes project conducted by the UK government, which began in 2013 and involves sequencing the whole genome of NHS patients. The project focuses on patients with diseases of particular interest, such as cancer, rare or infectious diseases. These genome sequences are anonymised and, with consent, shared with researchers, creating a sizable library of genomes which are linked to medical conditions and health records. These clinical samples allow researchers to investigate conditions that are associated with specific genomic traits. This allows the collation of large amounts of genomic data associated with a disease and allows rapid side-by-side comparison of genome data to uncover trends such as BRAF mutations in melanoma.

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