异柠檬酸脱氢酶1突变与人脑胶质瘤

Isocitrate dehydrogenase 1 mutations and human gliomas

癌症基因组学研究表明大部分WHO Ⅱ级、Ⅲ级胶质瘤及继发性胶质母细胞瘤(IV级)中,异柠檬酸脱氢酶1(isocitrate dehydrogenase1,IDH1)发生了新的点突变。IDH1突变发生在肿瘤早期,与预后关系密切。突变改变了IDH1酶活性,导致α-酮戊二酸和2-羟基戊二酸聚集。本文讨论了IDH1突变与胶质瘤发生和病理诊断的关系以及靶向治疗的潜在意义。

A recent cancer genome-sequencing project revealed that that novel point mutations in isocitrate dehydrogenase 1（IDH1） in the majority of gliomas at WHO Grade Ⅱ and Ⅲ and secondary glioblastomas at grade IV.IDH1 mutations are early events in the development of gliomas,and are related with prolonged survival in gliomas at various grades.Mutated IDH1 shows an altered catalytic activity that results in the elevated levels of α-ketoglutarate and 2-hydroxyglutarate.The correlations among the gliomas pathological diagnosis,tumor genesis,the therapeutic potential for targeting mutant IDH enzymes are discussed in this review.