RAF Mutation in Thyroid Cancer

Hi there, I’m Michael Yeh from UCLA Health Endocrine Surgery, and today I want to talk about the BRAF mutation in thyroid cancer—what it is, what it means, and how it may impact treatment and prognosis.

What is the BRAF Mutation?

When we talk about the BRAF mutation in thyroid cancer, we’re typically referring to the BRAF V600E mutation. BRAF is a proto-oncogene, which means it’s a gene that, when mutated, can become a driver of cancer. This particular mutation causes the BRAF protein to become overactive, sending strong signals for cells to divide and grow uncontrollably. It can also make cells more likely to invade surrounding tissues—one of the key hallmarks of cancer.

In short: BRAF V600E is a growth signal gone haywire.

In the field of cancer, there are two main categories of mutations: Somatic mutations and germline (inherited) mutations

The BRAF V600E mutation is an acquired (somatic) mutation, not an inherited one. That means:

It occurs only in the cancer cells.
It’s not present in every cell in your body.
It’s not passed down from your parents or to your children.

This kind of mutation happens over time as our cells age and repair themselves, and small errors slip into the DNA. These are common and part of how cancer can develop, but they don’t affect your whole genetic makeup.

How Common is it in Thyroid Cancer?

The BRAF V600E mutation plays a role in several cancers, including skin (melanoma), colorectal, and lung cancers. Remarkably, it is found in about 40% of all thyroid cancers, and in approximately 50% of papillary thyroid cancers—which is the most common type, accounting for over 90% of new thyroid cancer diagnoses in the U.S.

Does BRAF V600E Mean a Worse Prognosis?

This is where it gets interesting. About 10 years ago, we thought that having the BRAF V600E mutation meant a worse prognosis—that is, a higher chance of the cancer returning or causing death. But now, our understanding has evolved.

Most people with papillary thyroid cancer do very well. These cancers are often small, slow-growing, and rarely fatal. So, if half of papillary thyroid cancers have the BRAF V600E mutation, but 95% of these patients do great, then the mutation alone cannot be the full story when it comes to prognosis.

What Does Recent Research Show?

We’ve learned that the context matters. For example:

Older patients (age 55+) with the mutation tend to do slightly worse than younger patients.
Men with the BRAF mutation may also have a slightly worse prognosis than those without it.

This suggests that BRAF V600E doesn’t act in isolation—it interacts with other genetic and biological factors.

Today, in 2025, we understand that BRAF V600E mutation is usually not a major concern when it exists in isolation. However, if it occurs alongside other mutations—such as TERT or p53—that combination can signal a more aggressive cancer with a higher risk of recurrence or spread. We sometimes call these “double hits” or “late-hit mutations.”

The good news? These combinations are rare—present in only about 5% of thyroid cancers.

What If You Have the Mutation?

If your biopsy or surgical pathology report shows a BRAF V600E mutation, don’t panic. It does not mean you have an aggressive or untreatable cancer. Most patients with this mutation live completely normal, healthy lives.

And even in cases where the cancer is more aggressive, we now have targeted therapies that are designed specifically to block the effects of the BRAF mutation. These new treatments are showing exciting and encouraging results in patients who need them.

If you have further questions about the BRAF mutation or thyroid cancer, talk to a thyroid cancer specialist. Once again this is Michael Yeh from UCLA Health Endocrine Surgery, and thanks for watching.