BRAF mutation test by PCR
BRAF (B-Raf Proto-Oncogene, Serine/Threonine Kinase) is a proto-oncogene that encodes the B-Raf protein, which is part of cellular signaling pathways such as MAPK/ERK. This protein regulates cell growth and division. Mutations in the BRAF gene can lead to uncontrolled cell growth, contributing to tumor development. BRAF mutations play a key role in personalized cancer treatment, as their presence may indicate the possibility of using targeted therapy.
Mutations in BRAF result in its constitutive activation (e.g., the V600E mutation), which leads to continuous activation of the MAPK signaling pathway, stimulating cell proliferation and promoting cancer progression.
Role of BRAF in cancer
Mutations in the BRAF gene can be one of the causes of tumor growth and metastasis. One of the most well-known mutations — V600E — is associated with aggressive progression of several tumors.
Melanoma
- Approximately 50–60% of melanoma cases contain the BRAF V600E mutation, making it one of the most common targets for targeted therapy.
Colorectal cancer
- BRAF mutations are also found in some cases of colorectal cancer, especially in metastatic forms. This may be a marker of poor prognosis.
Thyroid cancer
- BRAF mutations are frequently found in anaplastic thyroid cancer, which is an aggressive form of the disease.
Lung cancer
- BRAF mutations are also detected in rare cases of small cell and non-small cell lung cancer.
Types of BRAF mutations
The most well-known BRAF mutation is V600E, but other mutations exist as well.
V600E - this is a substitution of valine (V) with glutamic acid (E) at position 600. This mutation is activating and leads to persistent activation of the MAPK pathway, promoting tumor growth.
Other mutations
V600K, V600D, and others may also occur in various types of cancer, though less frequently than V600E.
BRAF amplification — an increase in the number of BRAF gene copies, which may lead to higher protein levels and enhanced signaling pathway activity.
Predicting response to therapy
Melanoma
- The BRAF V600E mutation makes the tumor susceptible to BRAF inhibitors such as vemurafenib and dabrafenib. Combining with MEK inhibitors (e.g., trametinib) increases treatment efficacy.
Lung cancer
- For patients with a BRAF V600E mutation in lung cancer, targeted therapy with vemurafenib and trametinib may be effective.
Colorectal cancer
- BRAF mutations may indicate a poor prognosis and require more aggressive chemotherapy approaches, since targeted therapy against BRAF is not always effective in colorectal cancer.