9 Facts About the BRAF Gene Mutation

BRAF is a gene that locks down a specific protein called B-Raf. This protein helps send signals inside your cells that are related to cell growth. Everyone has this gene, and when it’s working properly, it’s an important part of how cells operate. But when BRAF is faulty in some way—sometimes known as “changed” or “mutated”—then it might work against the body, by allowing some cancers to grow or even playing a role in that growth process.

Although BRAF mutation and its connection to cancer was only identified in 2002, research done since then has pinpointed at least 30 different types of mutation that could be associated with cancers. The relationship between BRAF mutation and melanoma is particularly strong. The mutation doesn’t play much of a role in other common cancers, such as lung cancer.

About half of all melanomas have changes in the BRAF gene. For those who do have the mutation, recurrence rates may be a concern. Even after successful treatment of the initial melanoma, the gene mutation typically causes melanoma to start growing again eventually. Because of this, your doctor may suggest a more frequent screening schedule if you’ve had melanoma and carry the gene mutation.

If you have a mutation in your BRAF gene, melanoma cells will be making an altered form of protein that helps them grow. If that’s the case, you'll likely be treated with drugs that target this protein specifically. These meds are vemurafenib (Zelboraf) and dabrafenib (Tafinlar). They're designed to attack the BRAF protein directly, to reduce tumor size and slow its growth. Drugs that target the BRAF protein aren’t likely to work in patients whose melanomas have a normal BRAF gene.

In addition to BRAF, a gene called MEK may be a factor in your diagnosis and treatment. The MEK gene works together with BRAF, so your oncologist may add MEK inhibitors to your treatment plan. These drugs are called trametinib (brand name Mekinist) and cobimetinib (Cotellic), which have both been shown to shrink some melanomas that are associated with BRAF mutations. Commonly, a MEK inhibitor is combined with a BRAF inhibitor. This seems to shrink tumors for longer than either drug on its own. Keep in mind your treatment plan will be unique to you, based on what you and your doctor decide as the best course of action.

Genetic tests are usually performed using blood samples, although they might involve hair or skin. DNA can also be collected from a sample of cells, using a cheek swab. But the BRAF mutation can’t be pinpointed with any of these methods. Instead, it has to be done on a melanoma tumor tissue sample, which means you would need a biopsy. Sometimes, a biopsy is already done to verify the diagnosis and determine staging, so it’s possible you wouldn’t need a second biopsy for BRAF gene results.

Several gene mutations related to melanoma that may be part of your family’s gene history. For example, the CDKN2A gene, which regulates cell division, is considered the most common cause of inherited melanoma. The BRAF gene mutation, though, is often called a “non-inherited mutation,” which means you can have it even if no one else in your family did. It also means your kids won’t necessarily have it, just because it’s present in your DNA.

Although it’s most associated with melanoma, the BRAF mutation may play a part in thyroid cancer, non-small cell lung cancer, and colorectal cancer. About 10 percent of colorectal cancer patients have a BRAF gene mutation, according to a report in Biomarkers in Cancer. Several clinical trials are ongoing to try and figure out the best treatment options for those with colorectal cancer who also have the BRAF mutation.

Many clinical trials related to melanoma are taking place, with some that involve the BRAF gene mutation. Try visiting www.clinicaltrials.gov and searching “melanoma” for a list of relevant trials. Bring this list to the attention of your doctor, who can help you take the next steps.