BRAF is a gene that encodes the B-raf protein. BRAF plays an important role in the way that cell growth, cell proliferation, and cell differentiation are controlled. Cell growth is an increase in cell size, cell proliferation is an increase in the number of cells, and cell differentiation is the process in which immature (unspecialized) cells become mature (specialized) cells. If the BRAF gene has a mutation, the control system (signaling pathway) for these processes may not function properly. This can allow cells to grow abnormally and become cancer. Genes, like BRAF, that can cause normal cells to become tumor (tumour) cells are called oncogenes. The BRAF mutations found in colorectal (bowel) cancer are somatic, which means they occur in non-reproductive cells and are not hereditary.
The BRAF oncogene plays a role in several different cancers. BRAF mutations are present in approximately 10%-15% of colorectal cancers, 35% of melanomas, and more than 50% of thyroid papillary carcinomas. The majority of BRAF mutations are V600E mutations. Other mutations in BRAF do occur but they are rare. The incidence of BRAF mutation is higher in right-sided (proximal) colon cancers compared to left-sided (distal) colon cancers and rectal cancers.
BRAF is both a prognostic factor and a predictive biomarker. BRAF mutation status gives information about the usual course of disease (prognosis) and it predicts which treatments may be more or less effective against a particular colorectal (bowel) cancer, such as conventional chemotherapy drugs or targeted therapy with EGFR (epidermal growth factor receptor) inhibitors.
The recommended method of testing for BRAF mutation status is with a biopsy sample of cancer cells, either from the primary colorectal tumor or from tumor metastases in another part of the body (lymph node, liver, peritoneum). The cancer cells are treated in a laboratory to isolate the tumor DNA to be studied.
BRAF may also be tested in a blood sample by examining circulating tumor DNA (ctDNA) for BRAF mutations. This is called a liquid biopsy. BRAF may be tested individually, or as part of a multi-gene panel using next-generation sequencing (NGS). BRAF mutation testing is sometimes also called BRAF mutation analysis or BRAF gene sequencing.
If your result is reported as “BRAF wild-type” or “BRAF WT”, this means there is no BRAF mutation in your colorectal cancer (CRC). Wild-type is the normal state of the gene.
If your colon cancer or rectal cancer has a BRAF gene mutation, it will be reported as “BRAF mutant” or as the specific mutation, for example “BRAF V600E mutation”.
If your BRAF is wild-type (no mutation)
If your colorectal cancer has a BRAF gene mutation
There are ongoing clinical trials for treatments that specifically target BRAF wild-type and BRAF mutant metastatic colorectal cancer, including drugs already approved for use in the treatment of other BRAF mutant cancers. Talk to your oncology team about whether you could benefit from participation in a clinical trial.
If you have stage IV / metastatic colorectal cancer (mCRC), you should be tested for the BRAF biomarker.
A biomarker is a piece of information about your health. Biomarkers include your blood pressure, your blood type, and cholesterol or blood sugar levels measured in a blood test. The biomarkers of cancer are also known as tumor markers.