BRAF mutations are found in roughly half of melanomas.
Medications that target these mutations have significantly improved the survival rates of metastatic melanoma.
BRAF mutations are also present in some non-small cell lung cancers, colon cancers, and other tumor types.
Verywell / Jessica Olah
This article looks at what a BRAF mutation is and its frequency in different types of cancer.
It also looks at testing, treatment options, and recent advances.
You may hear the term “targetable mutation” or “actionable mutation.”
Verywell / Alison Czinkota
Proto-oncogenes are normal genes that code for proteins important in stimulating cell growth and division.
When mutated, proto-oncogenes become oncogenes.
These genes can be thought of as an accelerator on a car that is stuck in the on position.
When these genes are damaged, they allow abnormal cells to continue to grow and reproduce.
TheBRCA geneslinked to breast cancer are examples of tumor suppressor genes.
(At least one other mutation is needed for cancer to develop.)
Alone, the mutation can lead to the development of benign moles.
BRAF mutations associated with cancer are almost always acquired mutations.
They are present only in the cancer cells and not all of the cells in the body.
Acquired mutations are much more common in oncology.
Non-V600 BRAF Mutations
With lung adenocarcinoma, around 50% to 80% of BRAF mutations are non-V600 variants.
In colorectal cancer, 22% to 30% are non-V600 variants.
B-Raf proteins are part of a signaling pathway (RAF-MEK-ERK) that affects cell growth in several ways.
This pathway:
This pathway is very important in the womb as the embryo develops.
When continuously activated in an adult, it can result in uncontrolled growth of cells (cancer).
They are also continuously changing, developing new mutations that may allow them to escape our current treatments.
However, the frequency, as well as the response to BRAF inhibitors, varies.
BRAF mutations are an example of how cancer treatment is changing.
BRAF inhibitors, in contrast, are what are now considered “tumor agnostic” medications.
Reading studies about BRAF mutations can be confusing.
Hairy Cell Leukemia
BRAF mutations are relatively common withhairy cell leukemia.
The presence of a BRAF mutation can help distinguish hairy cell leukemia from other B cell lymphomas or leukemias.
Serous Ovarian Cancer
BRAF mutations are relatively common in people who have serous ovarian cancer.
It’s not yet known what the significance of the mutation might be with respect to treatment.
Testing is also important for those who do not have the mutation.
For example, using BRAF inhibitors in melanomaswithouta BRAF mutation may actually lead to progression of a tumor.
Methods
Several different methods of testing for BRAF are currently available.
DNA sequencing (eg.
next-generation sequencing) takes time but is the gold standard.
It can detect different types of BRAF mutations, as well as many other alterations that may be treatable.
A faster test (PCR) can be done, but only detects V600E mutations.
Tumor Testing vs.
Unfortunately, tissue biopsies are invasive and may not always be possible.
Discordance
The concept of discordance is an important one for people living with advanced cancer.
Some people may be aware that breast cancer can change.
The same is true with genomic alterations such as BRAF mutations.
A common scenario is with lung adenocarcinoma that progresses.
Cancers continually change and develop new mutations.
With melanoma, metastases are more likely to be BRAF positive than a primary tumor.
This stresses the importance of testing.
The presence of BRAF mutations may also provide information about the prognosis of a tumor.
Tumors that harbor BRAF mutations can behave differently clinically.
The combination also appears to work for a longer period of time.
There are now three BRAF inhibitors that have been approved.
These drugs directly attack the protein coded for by the mutated BRAF gene.
Among those treated, almost two-thirds of people with tumors found to be BRAF positive will respond.
Targeted therapy has a high chance of working, but only controls the disease for a while.
This is something referred to not as a cure, but a “durable response.”
Immunotherapy has a lower response rate, but sometimes a much longer duration of action.
Resistance
Unfortunately, most tumors become resistant to these targeted therapies in time.
That’s important as new therapies are developed to combat the disease.
Frequently Asked Questions
The BRAF gene provides instructions to the protein that manages cell growth.
The BRAF gene, found on chromosome 7, is responsible for cell growth.
However, not everyone has a mutation of the BRAF gene that contributes to cancer development.
“BRAF positive” means that your tumor has a mutation in the BRAF gene.
This gene controls a protein that stimulates cell growth.
Knowing your status can help ensure that your healthcare provider is providing the right treatment.
It’s possible, but not likely.
In very rare cases, BRAF mutations can be inherited, causing serious health problems.
No, they can’t go away, but treatment may help with managing their effects.
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