胶质瘤中的异柠檬酸脱氢酶突变

胶质母细胞瘤的基因组突变分析中发现的异柠檬酸脱氢酶（isocitrate dehydrogenase,IDH）突变对胶质瘤的认识具有突破性意义.随后,在胶质瘤中发现了IDH1的R132碱基和IDH2的R172碱基突变.IDH1突变较多的发生在WHOⅡ～Ⅲ级胶质瘤和继发胶质母细胞瘤中.这种突变改变了异柠檬酸脱氢酶的结构,从而使将异柠檬酸转化为α-酮戊二酸的能力丧失,而获得将α-酮戊二酸转化为D-2-羟基戊二酸这一新的酶活性.在临床中,IDH1和IDH2突变已经显示对胶质瘤患者有诊断和预后意义.同时,现今也发展了一些检测方法.

Isocitrate Dehydrogenase Mutations in Gliomas

The discovery of somatic mutations in the isocitrate dehydrogenase （IDH） enzymes through a genome-wide mutational analysis in glioblastoma represents a milestone in cancer biology. Heterozygous mutations in either the R132 residue of IDH1 or the R172 residue of IDH2 in human gliomas were recently highlighted. Heterozygous mutations in IDH1 occur in the majority of WHO grade II and grade III gliomas and secondary glioblastomas, leading to change of the enzyme structure, inactivation of the enzymatic activity by converting isocitrate （ICT） to ct-ketoglutarate （ot-KG） , thereby a newly acquired ability due to conversion of ct-KG to D-2-hydroxyglutarate （ D- 2-HG） . IDH1 and IDH2 mutations have shown diagnostic and prognostic value. Some detection methods have been developed.