The diagnostic role and clinical relevance of determination of BRAF status in brain tumors.

BRAF protein is a serine/threonine kinase that serves as an immediate downstream effector of the MAPK signaling cascade, a signal transduction pathway that modulates cell proliferation and survival. BRAF alterations leading to MAPK pathway activation have been identified in gliomas and glioneuronal tumors of the CNS. Whereas BRAF mutations have been found in a wide spectrum of CNS tumors, BRAF fusions have been almost exclusively found in pilocytic astrocytomas. BRAF fusion identification provides an additional help in the differential diagnosis of supratentorial gliomas. Although the prognostic significance of BRAF alterations in different CNS tumors is still under investigation, the evidence of BRAF-dependent MAPK-pathway activation in gliomas has moreover drawn attention to the potential use of MEK1/2 and RAF inhibitors in clinical neuro-oncology. Given the promising results of the therapeutic management of several cancer types, clinical studies investigating the suitability of such inhibitors for the therapy of gliomas are ongoing.