BRAF is a gene that gives instructions to make the BRAF protein, an enzyme that helps control how cells grow and divide. The BRAF protein is part of a signaling system in the cell known as the MAPK/ERK pathway, which normally functions as a switch to instruct cells when to grow and when to stop.
In healthy cells, this pathway turns on and off only when needed. However, mutations (changes) in the BRAF gene can make the protein stay switched on all the time. This causes cells to grow and divide too quickly, which can lead to cancer.
The most common BRAF mutation is called V600E. In this mutation, one building block of the gene (the amino acid valine, or “V”) is replaced by another (glutamic acid, or “E”) at position 600. This small change makes the BRAF protein continuously active. Other less common BRAF mutations, such as V600K and V600R, may also be seen in cancer.
BRAF mutations are found in various types of cancer. The exact frequency depends on the cancer type:
Melanoma: Approximately 50 to 60 percent of skin melanomas harbor a BRAF mutation, most commonly the V600E mutation. Other mutations, such as V600K or V600R, are less common.
Colorectal cancer: Approximately 5 to 10 percent of colorectal cancers have a BRAF mutation, typically the V600E variant. These tumors often have other special features, such as microsatellite instability (MSI) and the absence of KRAS mutations.
Papillary thyroid carcinoma: BRAF mutations are found in about 40 to 50 percent of papillary thyroid carcinomas, making it one of the most common genetic changes in this type of thyroid cancer.
Non-small cell lung cancer (NSCLC): BRAF mutations are less common in lung cancer, found in about 1 to 3 percent of lung adenocarcinomas.
Hairy cell leukemia: More than 95 percent of patients with hairy cell leukemia have a BRAF V600E mutation. This mutation is considered a defining feature of the disease.
Pathologists can test for BRAF mutations using different laboratory methods:
IHC is a test that uses antibodies to detect proteins in cells. If the BRAF gene is mutated, the abnormal protein it produces can sometimes be identified with this test.
PCR is a test that reads the genetic code of a gene to look for specific mutations. If a mutation is found, your pathology report may describe it as “detected” or “positive” and provide details about where in the gene the mutation occurred. If no mutation is found, it will be reported as “not detected” or “negative.”
NGS is a more advanced method that examines multiple genes simultaneously, including BRAF. NGS can detect common and rare mutations. If a mutation is found, your report may describe it as pathogenic (known to cause disease) or likely pathogenic. If no mutation is seen, the report will describe the result as negative.
Finding a BRAF mutation can be very important for treatment decisions. In cancers such as melanoma, colorectal cancer, thyroid cancer, and lung cancer, the presence of a BRAF mutation may make you eligible for targeted therapy drugs that specifically block the abnormal protein. These therapies are often more effective and cause fewer side effects than traditional chemotherapy.
Was my tumor tested for BRAF mutations?
If a BRAF mutation was found, which type was it?
Does the mutation make me eligible for targeted therapy?
How do these results affect my prognosis?
Do I need additional genetic tests, such as NGS, to look for other mutations?