L-2-Hydroxyglutarate: An Epigenetic Modifier and Putative Oncometabolite in Renal Cancer
作者： Eun-Hee Shim , Carolina B. Livi , Dinesh Rakheja , Jubilee Tan , Daniel Benson
DOI: 10.1158/2159-8290.CD-13-0696
关键词:
摘要: Through unbiased metabolomics, we identified elevations of the metabolite 2-hydroxyglutarate (2HG) in renal cell carcinoma (RCC). 2HG can inhibit 2-oxoglutaratre (2-OG) dependent dioxygenases which mediate epigenetic events including DNA and histone demethylation. accumulation, specifically D- enantiomer, result from gain function mutations isocitrate dehydrogenase (IDH1, IDH2) found several different tumors. In contrast, kidney tumors demonstrate L enantiomer (L-2HG). High reduced levels 5-hydroxymethylcytosine (5hmC) consistent with 2-HG mediated inhibition TET (Ten Eleven Translocation) enzymes convert 5-methylcystoine (5mC) to 5hmC. L-2HG elevation is part by expression (L2HGDH). L2HGDH reconstitution RCC cells lowers promotes 5hmC accumulation. Additionally, reduces methylation suppresses vitro tumor phenotypes. Our report identifies as an modifier putative oncometabolite cancer.
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