IDH1/2 mutations target a key hallmark of cancer by deregulating cellular metabolism in glioma |
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| Authors: | Chunzhi Zhang Lynette M. Moore Xia Li W. K. Alfred Yung Wei Zhang |
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| Affiliation: | Department of Pathology (C.Z., L.M.M., X.L., W.Z.); Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (W.K.A.Y.); Department of Radiation Oncology, Tianjin Huan Hu Hospital, Tianjin, China (C.Z.); Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi''an, China (X.L.) |
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| 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. |
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| Keywords: | glioma IDH1/2 mutation 2-hydroxyglutarate 2-HG metabolism |
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