期刊
NEURO-ONCOLOGY
卷 18, 期 1, 页码 16-26出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/neuonc/nov136
关键词
brain tumor metabolism; D-2-hydroxyglutarate; epigenetics; glioma genetics; isocitrate dehydrogenase mutations
资金
- V Foundation
- Accelerate Brain Cancer Cure Foundation
- Slomo and Cindy Silvian Foundation
- Voices Against Brain Cancer Foundation
- James S. McDonnell Foundation
- American Cancer Society Research Scholar Award [RSG-10-126-01-CCE]
- National Cancer Institute [5R01-CA140316, 1R01NS086943, P50-CA190991]
- [5T32CA074736-15]
- NATIONAL CANCER INSTITUTE [P50CA190991, R01CA140316, T32CA074736] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS086943] Funding Source: NIH RePORTER
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 alpha-ketoglutarate (alpha KG), but recurrent mutations at Arg(132) of IDH1 and Arg(172) of IDH2 confer a neomorphic enzyme activity that catalyzes reduction of alpha KG into the putative oncometabolite D-2-hydroxyglutate (D2HG). D2HG inhibits alpha KG-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.
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