title: The role of mutation of metabolism-related genes in genomic hypermethylation.
abstract: Genetic mutations, metabolic dysfunction, and epigenetic misregulation are commonly considered to play distinct roles in tumor development and maintenance. However, intimate relationships between these mechanisms are now emerging. In particular, mutations in genes for the core metabolic enzymes IDH, SDH, and FH are significant drivers of diverse tumor types. In each case, the resultant accumulation of particular metabolites inhibits TET enzymes responsible for oxidizing 5-methylcytosine, leading to pervasive DNA hypermethylation.
authors.affiliation: Genetics Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Waterfall
authors.affiliation: Genetics Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: J Keith
authors.initials: JK
authors.lastname: Killian
authors.affiliation: Genetics Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA. Electronic address: pmeltzer@mail.nih.gov.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Meltzer
mesh_terms: D019175:DNA Methylation; D049308:Dioxygenases / Q000037:antagonists & inhibitors; D005649:Fumarate Hydratase / Q000235:genetics*; D015894:Genome, Human; D005977:Glutarates / Q000378:metabolism; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: D005977:Glutarates; C019417:alpha-hydroxyglutarate; D007521:Isocitrate Dehydrogenase; D049308:Dioxygenases; D013385:Succinate Dehydrogenase; D005649:Fumarate Hydratase
keywords: Cancer; DNA methylation; FH; IDH; Metabolism; SDH