Ohba Shigeo, Hirose Yuichi
Department of Neurosurgery, Fujita Health University.
Neurol Med Chir (Tokyo). 2016;56(4):170-9. doi: 10.2176/nmc.ra.2015-0322. Epub 2016 Mar 10.
Mutations of the isocitrate dehydrogenase (IDH) genes are considered an important event that occurs at an early stage during gliomagenesis. The mutations often occur in grade 2 or 3 gliomas and secondary glioblastomas. Most IDH mutations are associated with codon 132 and 172 in IDH1 and IDH2 in gliomas, respectively. While IDH1 and IDH2 catalyze the oxidative decarboxylation of isocitrate to form α-ketoglutarate (α-KG), IDH1 and IDH2 mutations convert α-KG to 2-hydroxyglutarate (2-HG). The accumulation of oncometabolite 2-HG is believed to lead progenitor cells into gliomas, inhibiting several α-KG-dependent enzymes, including ten-eleven translocation enzymes, histone demethylases, and prolyl hydroxylases, although the mechanisms have not been fully revealed. Herein, we review the contribution of IDH1 and IDH2 mutations to gliomagenesis.
异柠檬酸脱氢酶（IDH）基因的突变被认为是胶质瘤发生早期阶段发生的一个重要事件。这些突变常发生在2级或3级胶质瘤以及继发性胶质母细胞瘤中。大多数IDH突变分别与胶质瘤中IDH1和IDH2的第132和172密码子相关。虽然IDH1和IDH2催化异柠檬酸的氧化脱羧形成α-酮戊二酸（α-KG），但IDH1和IDH2突变会将α-KG转化为2-羟基戊二酸（2-HG）。尽管其机制尚未完全阐明，但人们认为致癌代谢物2-HG的积累会使祖细胞发展为胶质瘤，抑制几种α-KG依赖性酶，包括十一-易位酶、组蛋白去甲基化酶和脯氨酰羟化酶。在此，我们综述IDH1和IDH2突变对胶质瘤发生的作用。
