摘要：

异柠檬酸脱氢酶1 和2（IDH1/2）基因突变主要发生于星形细胞瘤、间变型星形细胞瘤、少突胶质细胞瘤、间变型少突胶质细胞瘤、少突星形细胞瘤、间变型少突星形细胞瘤和继发性胶质母细胞瘤。IDH1/2 基因突变改变蛋白酶功能、消耗α-酮戊二酸和还原型烟酰胺腺嘌呤二核苷酸磷酸，从而产生致癌代谢物2-羟基戊二酸，2-羟基戊二酸在细胞内蓄积可引起一系列下游效应并最终导致上述胶质瘤发生。IDH1/2 基因突变及伴发的其他分子遗传学改变可用于胶质瘤的鉴别诊断。IDH1/2 基因突变也是上述胶质瘤有良好预后的独立预测因子。而针对IDH1/2 基因突变的分子靶向治疗也是目前胶质瘤治疗研究的热点。本文对近年来胶质瘤IDH1/2 基因突变研究进展简要概述。

关键词: 神经胶质瘤, 异柠檬酸脱氢酶, 基因, 肿瘤, 突变, 综述

Abstract:

The gene mutations of isocitrate dehydrogenase 1 and 2 (IDH1/2) mainly occur in astrocytoma, anaplastic astrocytoma, oligodendroglioma, anaplastic oligodendroglioma, oligoastrocytoma, anaplastic oligoastrocytoma and secondary glioblastoma. The IDH1/2 gene mutation can alter proteinase function, consume α-ketoglutarate and nicotinamide adenine dinucleotide phosphate-reduced (NADPH) and thus produce carcinogenic metabolite, 2-hydroxyglutarate. The intracellular accumulation of 2-hydroxyglutarate will induce a series of downstream effects which may result in the development of gliomas mentioned above. Both IDH1/2 mutations and other concomitant hereditary variations are biomarkers for differential diagnosis and IDH1/2 mutations are also independent factors for the prognosis of gliomas. The molecular targeting therapy for IDH1/2 mutations has become the research focus of glioma treatment. This review summarizes the recent progress of this field.

Key words: Glioma, Isocitrate dehydrogenase, Genes, neoplasm, Mutation, Review