软骨肿瘤异柠檬酸脱氢酶基因突变的研究进展

Research progress of isocitrate dehydrogenase(IDH)genetic mutations in cartilage tumors

软骨肿瘤是常见的原发性骨肿瘤,根据频发或特异的驱动基因变异可以对软骨肿瘤进行分子分型,从而更精准地指导临床诊疗。异柠檬酸脱氢酶(IDH)是一类代谢酶家族,广泛参与糖代谢、氨基酸代谢和脂类代谢过程。IDH1/IDH2突变后的代谢产物能够导致基因过甲基化和组蛋白修饰改变,进而诱发肿瘤。既往研究显示,良性和恶性软骨肿瘤中均存在一定比例的IDH1/IDH2突变,突变率约为51.4%,其中最常见的突变类型是IDH1 R132C,其他常见突变包括IDH1 R132G、IDH1 R132H、IDH2 R172G等。目前,IDH1/IDH2突变与软骨肿瘤预后之间的关系仍有待进一步研究。IDH突变靶向治疗可能是软骨肉瘤的新型治疗方法,多个IDH1/IDH2突变抑制剂正在进行Ⅰ/Ⅱ期临床试验中。本文旨在介绍近年来IDH基因突变与软骨肿瘤间关系的研究进展。

Cartilage tumor is a kind of common primary bone tumor.Cartilage tumors can be classified in molecular level ac⁃cording to frequent or recurrent mutations in driver genes,which can expedite development of the diagnostic and therapeutic strategies.Isocitrate dehydrogenase(IDH)is a metabolic enzyme family extensively involved in glucose,amino acid and lipid metabolism.Mutated IDH1/IDH2 can lead to gene hypermethylation and histone modification,which can further lead to onco⁃genesis.Recent researches indicated that mutation rates of IDH1/IDH2 in benign and malignant cartilage tumors were 51.4%.Most common mutation was IDH1 R132C,followed by IDH1 R132G、IDH1 R132H、IDH2 R172G.The relationship between cartilage tumors and IDH1/IDH2 genetic mutations requires further investigation.IDH mutations targeted therapy may be a new treatment for chondrosarcoma.Several IDH1/IDH2 mutation inhibitors are in phase I/II clinical trials.The purpose of this article is to report the research progress of the relationship between IDH genetic mutations and cartilage tumors.