期刊
ONCOGENE
卷 29, 期 49, 页码 6409-6417出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2010.444
关键词
IDH; mutations; cancer
The discovery of somatic mutations in the isocitrate dehydrogenase (IDH) enzymes through a genome-wide mutational analysis in glioblastoma represents a milestone event in cancer biology. The nature of the heterozygous, point mutations mapping to arginine residues involved in the substrate binding inspired several research teams to investigate their impact on the biochemical activity of these enzymes. Soon, it became clear that the mutations identified impaired the ability of IDH1 and IDH2 to catalyze the conversion of isocitrate to alpha-ketoglutarate (alpha KG), whereas conferring a gain of a novel enzymatic activity leading to the reduction of alpha KG to the metabolite D2-hydroxyglutarate (D-2HG). Across glioma as well as several hematologic malignancies, mutations in IDH1 and IDH2 have shown prognostic value. Several hypotheses implicating the elevated levels of D-2HG and tumorigenesis, and the therapeutic potential of targeting mutant IDH enzymes will be discussed. Oncogene (2010) 29, 6409-6417; doi:10.1038/onc.2010.444; published online 25 October 2010
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据