Activating mutations of the
serine threonine kinase v-RAF murine
sarcoma viral oncogene homologue B1 (BRAF), most commonly of the V600E type, are found in a wide range of human
neoplasms including primary and secondary
brain tumors. Therapeutic BRAF inhibitors have shown clinically meaningful activity, particularly in metastatic BRAF V600E mutated
melanoma including patients with
brain metastases. Therefore, in current neuropathological practice BRAF testing is of clinical importance in tissue samples of
melanoma brain metastases in order to identify cases amenable to
therapy with BRAF inhibitors. BRAF mutation testing may also add additional information for differential diagnosis of
primary brain tumors in selected situations, e.g., for differentiation of anaplastic
pleomorphic xanthoastrocytoma (BRAF V600E mutation in 65%) from
glioblastoma (BRAF V600E mutation in < 5%). The BRAF mutation status can be tested with
DNA-based methods and immunohistochemistry using a V600E mutation-specific antibody. In summary, at this point BRAF V600E testing is clinically indicated in relatively few cases of the daily clinical neuropathology practice, but has important predictive implications for patients with
melanoma brain metastases. Depending on the results of additional clinical studies, determination of BRAF mutation status may become clinically relevant also for
primary brain tumors such as
glioblastoma in the future.