脑胶质瘤中异柠檬酸脱氢酶突变的研究进展

Advances in IDH mutation in qlioma

异柠檬酸脱氢酶(isocitrate dehvdrogenase,IDH)是三羧酸循环的关键酶,催化异柠檬酸氧化脱羧生成α-酮戌二酸(α-ketoglutaric acid,α-KG),同时利用烟酰胺腺嘌呤二核苷酸(nicotinamide adeninedinudeotide,NAD^+)/烟酰胺腺嘌呤二核苷磷酸(nicotinamide adenine dinucleotide phosphate,NADP^+)作为辅助因子生成还原型NADH/NADPH。超过75%的低级别胶质瘤(WHO分级为Ⅱ和Ⅲ级)和90%的继发性成胶质细胞瘤中存在IDH基因突变,且主要突变位点为R132H(132位精氨酸突变为组氨酸)。IDH基因突变改变了胶质瘤的表观遗传学特征,使胶质瘤代谢重编程,破坏胶质瘤氧化还原稳态。以突变的IDH基因为治疗靶点能抑制胶质瘤的进展,可用于新的抗肿瘤药物的研发。

Isocitrate dehydrogenase （IDH） is a key enzyme in the tricarboxylic acid cycle, catalyzing the conversion of isocitric acid to α-ketoglutaric acid （α-KG）, using nicotinamide adenine dinucleotide （NAD＋）/ nicotinamide adenine dinucleotide phosphate （NADP＋） as its cofactor to produce NADH/NADPH. It has been recognized that more than 75% of low grade gliomas （WHO grade Ⅱ and Ⅲ） and 90% of secondary glioblastoma multiforme carry IDH gene mutation, with R132H mutation being predominant. IDH mutation may modulate epigenetic characteristics, reprogram cell metabolism, and perturb redox homeostasis of gliomas. Targeted inhibition of mutant IDH in glioma can suppress tumor progression and give birth to the novel anticancer medicines.