Liu Xiang, Ling Zhi-Qiang
Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou, P.R. China.
Histol Histopathol. 2015 Oct;30(10):1155-60. doi: 10.14670/HH-11-643. Epub 2015 Jul 6.
In recent years, frequent isocitrate dehydrogenase 1/2 (IDH1/IDH2) gene mutations were found in a variety of tumors, which specifically alter arginine residues of catalytic active site in IDH1/IDH2 and confer new enzymatic function of directly catalyzing alpha-ketoglutarate (α-KG) to R-2-hydroxyglutarate (2-HG). 2-HG could competitively inhibit α-KG-dependent enzymes and might therefore contribute to tumorigenesis. In addition, mutation status of IDH1/IDH2 is closely related to the progress and prognosis of certain tumors. Thus IDH1/IDH2 is considered to be a promising biomarker for early diagnosis and prognosis and targeted therapy. In this study, the current research on IDH1/IDH2 mutation, especially the mechanisms and clinical characteristics related to tumor, are reviewed.
近年来，在多种肿瘤中发现了频繁的异柠檬酸脱氢酶1/2（IDH1/IDH2）基因突变，这些突变特异性地改变了IDH1/IDH2催化活性位点的精氨酸残基，并赋予了直接将α-酮戊二酸（α-KG）催化为R-2-羟基戊二酸（2-HG）的新酶功能。2-HG可竞争性抑制α-KG依赖性酶，因此可能促进肿瘤发生。此外，IDH1/IDH2的突变状态与某些肿瘤的进展和预后密切相关。因此，IDH1/IDH2被认为是一种有前景的早期诊断、预后及靶向治疗生物标志物。本研究对目前IDH1/IDH2突变的研究，尤其是与肿瘤相关的机制和临床特征进行综述。
