{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Shim EH"],"funding":["NCATS NIH HHS","NCRR NIH HHS","NCI NIH HHS"],"pagination":["1290-8"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4286872"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["4(11)"],"pubmed_abstract":["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 that mediate epigenetic events, including DNA and histone demethylation. 2HG accumulation, specifically the d enantiomer, can result from gain-of-function mutations of isocitrate dehydrogenase (IDH1, IDH2) found in several different tumors. In contrast, kidney tumors demonstrate elevations of the l enantiomer of 2HG (l-2HG). High-2HG tumors demonstrate reduced DNA levels of 5-hydroxymethylcytosine (5hmC), consistent with 2HG-mediated inhibition of ten-eleven translocation (TET) enzymes, which convert 5-methylcytosine (5mC) to 5hmC. l-2HG elevation is mediated in part by reduced expression of l-2HG dehydrogenase (L2HGDH). L2HGDH reconstitution in RCC cells lowers l-2HG and promotes 5hmC accumulation. In addition, L2HGDH expression in RCC cells reduces histone methylation and suppresses in vitro tumor phenotypes. Our report identifies l-2HG as an epigenetic modifier and putative oncometabolite in kidney cancer.Here, we report elevations of the putative oncometabolite l-2HG in the most common subtype of kidney cancer and describe a novel mechanism for the regulation of DNA 5hmC levels. Our findings provide new insight into the metabolic basis for the epigenetic landscape of renal cancer."],"journal":["Cancer discovery"],"pubmed_title":["L-2-Hydroxyglutarate: an epigenetic modifier and putative oncometabolite in renal cancer."],"pmcid":["PMC4286872"],"funding_grant_id":["UL1 TR001120","R01 CA131272","UL1 RR025767","P30 CA054174","R01 NCI CA131272","KL2 TR001118","UL1RR025767","P30 CA013148","K08 CA138774"],"pubmed_authors":["Rea SL","Dutta S","Rakheja D","Kho EY","Ghosh AP","Tan J","Sudarshan S","Kirkman R","Velu S","Block K","Li Q","Benson D","Mishur RJ","Chenna B","Guo L","Parekh V","Bae S","Wei S","Livi CB","Johnson-Pais TL","Shim EH"],"additional_accession":[]},"is_claimable":false,"name":"L-2-Hydroxyglutarate: an epigenetic modifier and putative oncometabolite in renal cancer.","description":"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 that mediate epigenetic events, including DNA and histone demethylation. 2HG accumulation, specifically the d enantiomer, can result from gain-of-function mutations of isocitrate dehydrogenase (IDH1, IDH2) found in several different tumors. In contrast, kidney tumors demonstrate elevations of the l enantiomer of 2HG (l-2HG). High-2HG tumors demonstrate reduced DNA levels of 5-hydroxymethylcytosine (5hmC), consistent with 2HG-mediated inhibition of ten-eleven translocation (TET) enzymes, which convert 5-methylcytosine (5mC) to 5hmC. l-2HG elevation is mediated in part by reduced expression of l-2HG dehydrogenase (L2HGDH). L2HGDH reconstitution in RCC cells lowers l-2HG and promotes 5hmC accumulation. In addition, L2HGDH expression in RCC cells reduces histone methylation and suppresses in vitro tumor phenotypes. Our report identifies l-2HG as an epigenetic modifier and putative oncometabolite in kidney cancer.Here, we report elevations of the putative oncometabolite l-2HG in the most common subtype of kidney cancer and describe a novel mechanism for the regulation of DNA 5hmC levels. Our findings provide new insight into the metabolic basis for the epigenetic landscape of renal cancer.","dates":{"release":"2014-01-01T00:00:00Z","publication":"2014 Nov","modification":"2020-10-31T08:14:19Z","creation":"2019-03-27T01:42:55Z"},"accession":"S-EPMC4286872","cross_references":{"pubmed":["25182153"],"doi":["10.1158/2159-8290.CD-13-0696","10.1158/2159-8290.cd-13-0696"]}}