New Molecular Considerations for Glioma: IDH, ATRX, BRAF, TERT, H3 K27M

• Published in: Current Neurology and Neuroscience Reports Vol. 17; no. 2; p. 19
• Main Authors: Karsy, Michael, Guan, Jian, Cohen, Adam L., Jensen, Randy L., Colman, Howard
• Format: Journal Article Book Review
• Language: English
• Published: New York Springer US 01.02.2017; Springer Nature B.V
• Subjects: Brain Neoplasms - genetics; DNA Helicases - genetics; Genomics; Glioma - classification; Glioma - diagnosis; Glioma - genetics; Histones - genetics; Humans; Isocitrate Dehydrogenase - genetics; Medicine; Medicine & Public Health; Mutation; Neuro-Oncology (LE Abrey; Neurology; Neurosciences; Nuclear Proteins - genetics; Proto-Oncogene Proteins B-raf - genetics; Section Editor; Telomerase - genetics; Topical Collection on Neuro-Oncology; X-linked Nuclear Protein; BRAF; Glioma; TERT; IDH; H3K27M; ATRX
• ISSN: 1528-4042; 1534-6293
• DOI: 10.1007/s11910-017-0722-5

Purpose of Review This review will discuss the role of several key players in glioma classification and biology, namely isocitrate dehydrogenase 1 and 2 (IDH1/2), alpha thalassemia/mental retardation syndrome X-linked (ATRX), B-Raf (BRAF), telomerase reverse transcriptase (TERT), and H3K27M. Recent Findings IDH1/2 mutation delineates oligoden-droglioma, astrocytoma, and secondary glioblastoma (GBM) from primary GBM and lower-grade gliomas with biology similar to GBM. Additional mutations including TERT, 1p/19q, and ATRX further guide glioma classification and diagnosis, as well as pointing directions toward individualized treatments for these distinct molecular subtypes. ATRX and TERT mutations suggest the importance of telomere maintenance in gliomagenesis. BRAF alterations are key in certain low-grade gliomas and pediatric gliomas but rarely in high-grade gliomas in adults. Histone mutations (e.g., H3K27M) and their effect on chromatin modulation are novel mechanisms of cancer generation and uniquely seen in midline gliomas in children and young adults. Summary Over the past decade, a remarkable accumulation of knowledge from the genomic study of gliomas has led to reclassification of tumors, new understanding of oncogenic mechanisms, and novel treatment strategies.