Mutations in the BRAF gene can cause normal cells to become cancerous. BRAF mutations are most commonly found in melanomas, but can occur in other forms of cancer. Not all mutations in BRAF cause cancer.

What is BRAF?

BRAF is a gene found on chromosome seven that encodes a protein also called BRAF. This protein plays a role in cell growth by sending signals inside the cell promoting, among other functions, cell division.

What is a BRAF mutation?

A BRAF mutation is a spontaneous change in the BRAF gene that makes it work incorrectly. A mutation causes the gene to turn on the protein and keep it on, which means certain cells get ongoing signals to keep dividing and no instructions on when to stop. This can lead to development of a tumor.

Scientists have identified many different types of BRAF mutations. One of the most common types is the BRAF V600E mutation. The name V600E describes the nature and location of the mutation:

• V and E represent the amino acids (building blocks of protein) that mutated. In this case, valine (V) got replaced by glutamic acid (E).
• 600 refers to the location of the mutation: amino acid number 600 inside the protein.

Different mutations in BRAF may be sensitive to different targeted therapies. Some mutations in BRAF aren’t sensitive to any particular targeted therapies.

What is the relationship between BRAF mutation and cancer?

Some mutations in BRAF cause cancer in combination with additional mutations or other factors. BRAF mutations can also cause cancers to grow more quickly than they would otherwise, either alone or in combination with additional mutations.

The cancers associated with the BRAF gene mutation are not specific to one part of the body or a certain cell type. These cancers include:

• Melanoma (about half of all melanomas have the BRAF gene mutation)
• Hairy cell leukemia
• Non-Hodgkin lymphoma
• Thyroid cancer
• Ovarian cancer
• Lung adenocarcinoma
• Colorectal cancer
• Certain brain cancers, including glioblastoma, pilocytic astrocytoma, and pediatric low-grade glioma

Is BRAF mutation hereditary?

In most cases, a BRAF mutation identified in cancer developed at some point throughout a person’s life. In this situation, the mutation affects only the cells where the change has occurred and cannot be passed on to your children. In a few very rare cases, BRAF mutations can be inherited (passed on from a parent). If a mutation is present at birth, it could affect multiple cells in the body, causing significant health issues.

How do I get tested for a BRAF mutation?

If you have a tumor, your oncologist may recommend analyzing the tumor’s DNA to see if it has a BRAF mutation. He or she will collect a sample of the tumor tissue through a biopsy and send it to a lab for genetic testing. The test results will show if the sample is positive or negative for the BRAF mutation, as well as the specific type of mutation. Biopsies are surgeries that can be difficult to perform on certain tumors because of their location, so a biopsy may not always be possible.

If biopsy is not an option, your doctor may recommend a blood test instead. It is less invasive and quicker, but it identifies only certain types of BRAF mutations and doesn’t offer as much detail as a genetic test.

A BRAF blood test could be an option if you don’t have a tumor but are eligible to be tested due to family history or other risk factors that make your doctor suspicious for a BRAF mutation.

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What does it mean if I have a BRAF mutation?

Knowing that you have a BRAF mutation will help your oncologist select appropriate cancer therapies. The presence of a BRAF mutation gives your doctors clues about:

• Best medicines to target the cancer cells
• How fast the tumor might grow and how large it might get
• How the cancer might respond to treatments such as chemotherapy and radiation therapy

It is equally important to know if you do not have a BRAF mutation. Using BRAF-targeting treatments on a tumor that does not have the mutation can have the opposite effect on tumor growth.

Treatments for BRAF-Mutated Tumors

Thanks to better understanding of the role of the BRAF gene in tumor growth, scientists have developed targeted medicines called BRAF inhibitors that interfere with the way the B-Raf protein signals the cell to multiply and grow. This doesn’t kill cancer cells, but it helps slow down the tumor growth, although not permanently.

There are several BRAF inhibitors that have been approved for use on certain tumors, including dabrafenib, encorafenib and vemurafenib.

Combination Treatments

B-Raf protein is part of a larger mechanism called the RAS-RAF-MEK-ERK pathway. This pathway helps regulate how cells grow, multiply and survive. When any part of this pathway is overactive inside a tumor, it is helping the cancer grow and potentially spread.

For certain tumors, BRAF inhibitors alone can offer good results. In other cases, your oncologist may recommend the use of a BRAF inhibitor together with another drug or several drugs that interfere with the RAS-RAF-MEK-ERK pathway. BRAF inhibitors are often used together with MEK inhibitors, such as trametinib, binimetinib, selumetinib or cobimetinib, which address a different part of the pathway.

Sometimes, immunotherapy can be used in combination with BRAF and MEK inhibitors. Immunotherapy engages your immune system to help fight the cancer. An immunotherapy treatment called immune checkpoint inhibitors works by helping unleash the immune response onto the tumor cells. Your immune system has mechanisms to control how strongly it responds to threats, so as to not damage healthy cells in the process. Checkpoint inhibitors can turn off this mechanism to amplify the immune response to the tumor.