Role of isocitrate dehydrogenase 1/2 (IDH 1/2) gene mutations in human tumors

Xiang Liu and Zhi-Qiang Ling

Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou, P.R. China.

Offprint requests to: Zhi-Qiang Ling, M.D, Ph.D, Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, No.38 Guangji Rd., Banshanqiao District, Hangzhou 310022, China. e-mail: lingzq@zjcc.org.cn or lingzq@hotmail.com

Summary. 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. Histol Histopathol 30, 1155-1160 (2015)

Key words: Isocitrate dehydrogenase 1/2 (IDH1/IDH2), Mutation, Methylation, Metabolism, Tumorigenesis

DOI: 10.14670/HH-11-643