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Neuro Oncol. 2013 Sep;15(9):1114-26. doi: 10.1093/neuonc/not087. Epub 2013 Jul 21.

IDH1/2 mutations target a key hallmark of cancer by deregulating cellular metabolism in glioma.

Author information

1
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Abstract

Isocitrate dehydrogenase (IDH) enzymes have recently become a focal point for research aimed at understanding the biology of glioma. IDH1 and IDH2 are mutated in 50%-80% of astrocytomas, oligodendrogliomas, oligoastrocytomas, and secondary glioblastomas but are seldom mutated in primary glioblastomas. Gliomas with IDH1/2 mutations always harbor other molecular aberrations, such as TP53 mutation or 1p/19q loss. IDH1 and IDH2 mutations may serve as prognostic factors because patients with an IDH-mutated glioma survive significantly longer than those with an IDH-wild-type tumor. However, the molecular pathogenic role of IDH1/2 mutations in the development of gliomas is unclear. The production of 2-hydroxyglutarate and enhanced NADP+ levels in tumor cells with mutant IDH1/2 suggest mechanisms through which these mutations contribute to tumorigenesis. Elucidating the pathogenesis of IDH mutations will improve understanding of the molecular mechanisms of gliomagenesis and may lead to development of a new molecular classification system and novel therapies.

KEYWORDS:

2-HG; 2-hydroxyglutarate; IDH1/2 mutation; glioma; metabolism

PMID:
23877318
PMCID:
PMC3748922
DOI:
10.1093/neuonc/not087
[Indexed for MEDLINE]
Free PMC Article

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