The Diagnostic Role and Clinical Relevance of Determination of Braf Status in Brain Tumors

Abstract

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.

KEYWORDS::

• BRAF mutations
• CNS
• FISH
• glioma
• immunohistochemistry
• KIAA1549–BRAF fusion
• MAPK
• neuropathology
• pilocytic astrocytoma

Acknowledgments

Special thanks to M Badiali (Cagliari, Italy) and P Niehusmann (Bonn, Germany) for their support in preparing Figure 1.

Financial&competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.