The role of mutation of metabolism-related genes in genomic hypermethylation

Joshua J Waterfall; J Keith Killian; Paul S Meltzer

doi:10.1016/j.bbrc.2014.08.003

The role of mutation of metabolism-related genes in genomic hypermethylation

Biochem Biophys Res Commun. 2014 Dec 5;455(1-2):16-23. doi: 10.1016/j.bbrc.2014.08.003. Epub 2014 Aug 8.

Authors

Joshua J Waterfall¹, J Keith Killian¹, Paul S Meltzer²

Affiliations

¹ Genetics Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
² Genetics Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA. Electronic address: [email protected].

PMID: 25111818
DOI: 10.1016/j.bbrc.2014.08.003

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.

Keywords: Cancer; DNA methylation; FH; IDH; Metabolism; SDH.

Publication types

Research Support, N.I.H., Intramural
Review

MeSH terms

DNA Methylation*
Dioxygenases / antagonists & inhibitors
Fumarate Hydratase / genetics*
Genome, Human
Glutarates / metabolism
Humans
Isocitrate Dehydrogenase / genetics*
Isocitrate Dehydrogenase / metabolism
Mutation*
Neoplasms / genetics*
Succinate Dehydrogenase / genetics*

Substances

Glutarates
alpha-hydroxyglutarate
Isocitrate Dehydrogenase
Dioxygenases
Succinate Dehydrogenase
Fumarate Hydratase

Grants and funding

Intramural NIH HHS/United States