异柠檬酸脱氢酶突变和神经胶质瘤

Isocitrate dehydrogenase mutations and gliomas

异柠檬酸脱氢酶(IDHs)单密码子发生的突变与胶质瘤的发生发展密切相关。目前认为IDHs的突变使其原有的酶活性丧失,但却能将α-酮戊二酸(α-KG)转变为双加氧酶抑制剂——2-羟戊二酸(2-HG),导致HIF-1α的表达增加和全基因组表观遗传学的改变,从而诱导神经胶质瘤的发生。自2008年IDH1突变在胶质瘤中被发现以来,对这种肿瘤相关代谢分子的突变研究越来越多。本文综述近年来关于IDHs突变在胶质瘤的筛查、鉴别诊断、预后及治疗方面的研究进展。

Single-codon mutations of isocitrate dehydrogenase（IDHs） are related to the tumorgenesis and development of glioma. IDHs mutations cause loss of native enzymatic activities and confer activity of converting α-KG to 2-hydroxyglutarate（2-HG） which is an inhibitor of dioxygenase, and then induce the high expression of HIF-1α gene and epigenetic changes in the whole genomics leading to the gliomagenesis. After IDH1 mutation was identified in glioma in 2008, much more work about this cancer-related metabolic molecular had been carried out. We review these advances of IDHs mutations in glioma＇s screening, diagnosis, prognosis and potential targeted drug therapy.