BRAF testing is a diagnostic procedure used in oncology to identify specific genetic alterations within tumors. The test analyzes the deoxyribonucleic acid (DNA) of cancer cells for mutations in the BRAF gene, a component of a cellular signaling pathway. Identifying these changes helps oncologists determine if a patient’s cancer will respond to specialized targeted therapies. This shifts the treatment approach from generalized chemotherapy to a more personalized, molecularly-driven strategy.
Understanding the BRAF Gene and Mutation
The BRAF gene provides instructions for making the B-Raf protein, a type of enzyme called a kinase. B-Raf acts as a molecular switch within the Mitogen-Activated Protein Kinase (MAPK) signaling pathway, which controls cell processes like growth and division. Normally, B-Raf is activated only when a cell needs to grow, ensuring regulated behavior.
A mutation in the BRAF gene changes the B-Raf protein’s structure, causing it to be constantly “switched on.” The most frequent mutation is V600E, accounting for over 90% of all BRAF mutations in human cancers. This change occurs when the amino acid Valine (V) at position 600 is replaced by Glutamic acid (E). This constant activation leads to uncontrolled signaling down the MAPK pathway, driving the rapid growth characteristic of cancer.
These BRAF mutations are overwhelmingly somatic, meaning they are acquired during a person’s lifetime and are present only in the cancer cells. They are not inherited from a parent or present in every cell of the body. This specific genetic change transforms the BRAF gene into an oncogenic driver, making it a target for specialized drug intervention.
When and Why This Specific Test is Necessary
The primary reason for BRAF testing is to identify candidates for targeted therapy, which directly attacks the cancer’s specific molecular defect. Oncologists typically order the test for patients diagnosed with advanced or metastatic cancer where BRAF mutations are known to occur and targeted drugs are approved. Testing is a standard part of the initial workup for several tumor types, as the results influence the first-line treatment decision.
BRAF testing is routinely performed for the following cancers:
- Malignant melanoma: Mutations occur in 40% to 50% of cases. For unresectable or metastatic melanoma, knowing the BRAF status is mandatory because targeted therapies offer high response rates and improved survival.
- Non-small cell lung cancer (NSCLC): The V600E mutation is found in 1% to 3% of patients.
- Colorectal cancer (CRC): Mutations are present in 5% to 10% of cases and often indicate a more aggressive disease course. Status guides targeted treatment and predicts response to certain antibody therapies.
- Thyroid cancers: The test is standard for papillary and anaplastic thyroid cancers, where the V600E mutation is highly prevalent and signals a potentially more aggressive prognosis.
The Testing Process and Sample Collection
BRAF testing is conducted using a sample of the patient’s tumor tissue or blood. The most common sample type is formalin-fixed, paraffin-embedded (FFPE) tissue, often leftover from a biopsy or surgery. Pathologists select the area of the tissue block with the highest concentration of tumor cells, typically requiring 10% to 50% tumor content for accurate results.
Less invasive options, known as liquid biopsies, are becoming more common, especially for patients with advanced disease or when a tissue biopsy is difficult. A liquid biopsy uses a blood sample to detect circulating tumor DNA (ctDNA), which is genetic material shed by cancer cells into the bloodstream. This method can provide a faster turnaround time than tissue-based testing, which helps expedite treatment initiation.
In the laboratory, techniques like Polymerase Chain Reaction (PCR) and Next-Generation Sequencing (NGS) are used to detect the mutation. PCR is fast and sensitive for detecting the specific V600E mutation. NGS is a broader method that sequences larger portions of the gene to detect V600E, less common BRAF mutations, and other cancer-related genes simultaneously. Turnaround time varies, ranging from 3 to 5 days for rapid PCR tests to up to two weeks for comprehensive NGS panels.
Interpreting BRAF Test Results for Treatment Planning
A “positive” BRAF test result indicates a mutation has been detected, opening the door to targeted therapy options. The V600E mutation is the primary target for BRAF inhibitors, such as vemurafenib, dabrafenib, and encorafenib. These medications work by directly blocking the activity of the mutated, overactive B-Raf protein, shutting down the uncontrolled growth signal.
A positive result might also reveal less common mutations (e.g., V600K, V600R, or V600D), which often respond to the same BRAF inhibitors. A “negative” result, or BRAF wild-type, means the specific mutation was not found. This result is important because it indicates the patient will not benefit from a BRAF inhibitor, necessitating a different treatment path and preventing the use of ineffective drugs that could cause unnecessary side effects.
For many cancers, especially advanced melanoma, the standard of care is to use a BRAF inhibitor combined with a MEK inhibitor. MEK is the protein immediately downstream of B-Raf in the MAPK pathway. Combining both inhibitors, such as trametinib, cobimetinib, or binimetinib, provides a more complete block of the growth signal. This dual blockade improves response rates, delays the development of drug resistance, and often reduces certain side effects associated with using a BRAF inhibitor alone.