BRAF testing is employed in oncology to identify specific alterations within a patient’s tumor. The information gathered from BRAF testing helps healthcare providers make informed decisions about the most suitable treatment options. It helps predict how quickly a cancer might grow and whether targeted therapies are likely to be beneficial.
Understanding the BRAF Gene and Its Role in Cancer
The BRAF gene, located on chromosome 7, provides instructions for creating a protein called B-Raf. This protein functions as a serine/threonine kinase, playing a role in transmitting chemical signals from outside the cell to its nucleus. This signaling pathway, known as the RAS/MAPK pathway, regulates several important cellular processes, including cell growth, division, and maturation.
When the BRAF gene undergoes a mutation, it can lead to the production of an abnormal BRAF protein that is continuously active. This constant activation sends unchecked signals for cells to divide and grow. One of the most common BRAF mutations is the V600E mutation, where the amino acid valine (V) at position 600 is replaced by glutamic acid (E). This specific change causes the BRAF protein to be perpetually “on,” significantly contributing to tumor formation and potentially faster cancer growth.
The Purpose and Process of BRAF Testing
BRAF testing detects specific mutations in the BRAF gene that drive cancer growth, which can inform treatment decisions. This test is commonly performed for several cancer types where BRAF mutations are known to occur. For instance, the V600E mutation is found in about 50% of melanomas, 10-15% of colorectal cancers, and up to half of papillary thyroid cancers. Additionally, these mutations are observed in a smaller percentage of non-small cell lung cancers, ovarian cancers, and certain brain tumors.
BRAF testing typically involves analyzing a sample of tumor tissue, which can be obtained through a biopsy or during surgery to remove the tumor. In cases where a tissue biopsy is not feasible, such as with certain hard-to-reach tumors, a liquid biopsy using a blood sample may be an alternative. Laboratory analysis often involves genetic sequencing techniques, such as next-generation sequencing or PCR amplification, to identify specific BRAF gene changes, particularly at codon 600. The pathologist examines the tissue section to ensure a sufficient percentage of tumor cells for accurate DNA extraction and mutation detection.
Interpreting BRAF Test Results and Treatment Implications
BRAF test results indicate whether a specific mutation in the BRAF gene is present in the tumor cells. A “BRAF-mutated” result, such as the BRAF V600E positive, signifies the presence of the altered gene. Conversely, a “BRAF wild-type” result means that the common BRAF mutations, particularly V600E, were not detected.
For patients with a BRAF mutation, particularly V600E, targeted therapies are available that specifically interfere with the abnormal BRAF protein. These medications, known as BRAF inhibitors (e.g., vemurafenib, dabrafenib, encorafenib), bind to the mutated BRAF protein, blocking the uncontrolled cell growth signals. Combining BRAF inhibitors with MEK inhibitors (e.g., trametinib, cobimetinib, binimetinib), which act further downstream in the same signaling pathway, can provide a more complete blockade of the pathway. This combination therapy has been shown to improve treatment response and survival for patients with BRAF-mutant melanoma, and can delay resistance. For patients with BRAF wild-type results, other treatment approaches, such as chemotherapy or immunotherapy, are considered, as BRAF-targeted therapies would not be effective.