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

  • Neuro-Oncology (LE Abrey, Section Editor)
  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

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.

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Authors and Affiliations

  1. Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, UT, USA

    Michael Karsy, Jian Guan, Randy L. Jensen & Howard Colman

  2. Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

    Adam L. Cohen, Randy L. Jensen & Howard Colman

  3. Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA

    Adam L. Cohen

  4. Department of Neurosurgery, The University of Utah, 175 North Medical Dr. East, Salt Lake City, UT, 84132, USA

    Howard Colman

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Michael Karsy and Jian Guan declare that they have no conflict of interest.

Adam L. Cohen reports grants from Novartis, Genentech, Merrimack, and BMS.

Randy L. Jensen reports personal fees from Pharmacokinesis and Medtronic.

Howard Colman has received advisory board fees from Roche, Genentech, Upsher-Smith, Oxigene, CytRx, Omniox, and Insys, and grants from Plexxikon and Newlink Genetics.

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Karsy, M., Guan, J., Cohen, A.L. et al. New Molecular Considerations for Glioma: IDH, ATRX, BRAF, TERT, H3 K27M. Curr Neurol Neurosci Rep 17, 19 (2017). https://doi.org/10.1007/s11910-017-0722-5

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