July 1, 2023

What is BRAF?

BRAF is a gene that provides instructions for making the BRAF protein, a kinase enzyme that is part of the MAPK/ERK signaling pathway. This pathway plays an important role in the regulation of cell growth and division.

What is a gene?

Each cell in your body contains a set of instructions that tell the cell how to behave. These instructions are written in a language called DNA and the instructions are stored on 46 chromosomes in each cell. Because the instructions are very long, they are broken up into sections called genes. Each gene tells the cell how to produce a piece of the machine called a protein.

All genes are made of molecules called bases. There are four bases (A, T, G, and C) that make up the genetic code. The order of the four bases determines which proteins are made.

How does BRAF cause cancer?

In normal, healthy cells, the BRAF protein works with other proteins in the MAPK/ERK pathway to regulate cell growth and proliferation. However, a change in the BRAF gene can cause the BRAF protein to behave abnormally. The most common mutation is the V600E mutation, where a valine (V) is substituted with a glutamic acid (E) at position 600. This mutation causes the protein to be continuously activated, leading to uncontrolled cell growth and division.

What types of cancers have BRAF mutations?

BRAF mutations can be found in various types of cancer. Some of the most common cancers associated with BRAF mutations include:

  • Melanoma: BRAF mutations are highly prevalent in melanoma, particularly the V600E mutation. It is estimated that around 50-60% of cutaneous melanomas have BRAF mutations. Other BRAF mutations, such as V600K and V600R, are also found but less frequently.
  • Colorectal cancer: BRAF mutations, including the V600E mutation, occur in a subset of colorectal cancers, typically in tumors that exhibit specific characteristics, such as microsatellite instability (MSI) and the absence of KRAS mutations. Approximately 5-10% of colorectal cancer cases harbor BRAF mutations.
  • Papillary thyroid carcinoma: BRAF mutations, specifically the V600E mutation, are commonly detected in papillary thyroid carcinoma, accounting for a significant proportion of cases. It is estimated that 40-50% of papillary thyroid carcinomas carry BRAF mutations.
  • Non-small cell lung cancer (NSCLC): While BRAF mutations are less frequent in NSCLC compared to melanoma and papillary thyroid carcinoma, they can still occur, particularly in lung adenocarcinomas. The prevalence of BRAF mutations in NSCLC is relatively low, around 1-3%.
  • Hairy cell leukemia (HCL): BRAF mutations, primarily the V600E mutation, are highly prevalent in HCL. Over 95% of patients with HCL carry the BRAF V600E mutation, making it a defining characteristic of this type of leukemia.

How do doctors test for BRAF mutations?

Immunohistochemistry (IHC)

Immunohistochemistry (IHC) is a special type of test that allows pathologists to see the kinds of proteins being made by a cell. Cells with a mutation in the BRAF gene make a BRAF protein that is different from normal cells. Immunohistochemistry can be used to see cells making this abnormal BRAF protein. Positive or reactive means that the tumour cells in your tissue sample are making an abnormal BRAF protein. Negative or non-reactive means that no abnormal BRAF protein was found.

Polymerase chain reaction (PCR)

Polymerase chain reaction (PCR) is a special test that allows pathologists to analyze the bases in one or more genes. By reading the bases in a gene, your pathologist can find cancer-causing mutations.

If a mutation is found in the BRAF gene it will be described in your report as detected or positive. Your report may also say where in the gene the mutation was found. If no mutation is found it will be described in your report as not detected or negative.

Next-generation sequencing (NGS)

Next-generation sequencing (NGS) is a special test used to analyze a large number of genes at the same time. NGS is commonly used to look for mutations in the BRAF gene and other genes that are known to cause cancer.

If a mutation is found it will be described as positive. The location and type of mutation may also be described in your report. A mutation known to cause cancer may be described as pathogenic or likely pathogenic. If no mutation is found, the results will be described as negative.

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