Isocitrate dehydrogenase mutations in gliomas.

Published

Journal Article (Review)

Over the last decade, extraordinary progress has been made in elucidating the underlying genetic causes of gliomas. In 2008, our understanding of glioma genetics was revolutionized when mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) were identified in the vast majority of progressive gliomas and secondary glioblastomas (GBMs). IDH enzymes normally catalyze the decarboxylation of isocitrate to generate α-ketoglutarate (αKG), but recurrent mutations at Arg(132) of IDH1 and Arg(172) of IDH2 confer a neomorphic enzyme activity that catalyzes reduction of αKG into the putative oncometabolite D-2-hydroxyglutate (D2HG). D2HG inhibits αKG-dependent dioxygenases and is thought to create a cellular state permissive to malignant transformation by altering cellular epigenetics and blocking normal differentiation processes. Herein, we discuss the relevant literature on mechanistic studies of IDH1/2 mutations in gliomas, and we review the potential impact of IDH1/2 mutations on molecular classification and glioma therapy.

Full Text

Duke Authors

Cited Authors

  • Waitkus, MS; Diplas, BH; Yan, H

Published Date

  • January 2016

Published In

Volume / Issue

  • 18 / 1

Start / End Page

  • 16 - 26

PubMed ID

  • 26188014

Pubmed Central ID

  • 26188014

Electronic International Standard Serial Number (EISSN)

  • 1523-5866

Digital Object Identifier (DOI)

  • 10.1093/neuonc/nov136

Language

  • eng

Conference Location

  • England