title: IDH1/2 mutations target a key hallmark of cancer by deregulating cellular metabolism in glioma.
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.
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Chunzhi
authors.initials: C
authors.lastname: Zhang
authors.forename: Lynette M
authors.initials: LM
authors.lastname: Moore
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: W K Alfred
authors.initials: WK
authors.lastname: Yung
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism*; D005910:Glioma / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D009154:Mutation
chemical_list: C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
keywords: 2-HG; 2-hydroxyglutarate; IDH1/2 mutation; glioma; metabolism