Integrative modelling of tumour DNA methylation quantifies the contribution of metabolism.

Journal Article (Journal Article)

Altered DNA methylation is common in cancer and often considered an early event in tumorigenesis. However, the sources of heterogeneity of DNA methylation among tumours remain poorly defined. Here we capitalize on the availability of multi-platform data on thousands of human tumours to build integrative models of DNA methylation. We quantify the contribution of clinical and molecular factors in explaining intertumoral variability in DNA methylation. We show that the levels of a set of metabolic genes involved in the methionine cycle is predictive of several features of DNA methylation in tumours, including the methylation of cancer genes. Finally, we demonstrate that patients whose DNA methylation can be predicted from the methionine cycle exhibited improved survival over cases where this regulation is disrupted. This study represents a comprehensive analysis of the determinants of methylation and demonstrates the surprisingly large interaction between metabolism and DNA methylation variation. Together, our results quantify links between tumour metabolism and epigenetics and outline clinical implications.

Full Text

Duke Authors

Cited Authors

  • Mehrmohamadi, M; Mentch, LK; Clark, AG; Locasale, JW

Published Date

  • December 14, 2016

Published In

Volume / Issue

  • 7 /

Start / End Page

  • 13666 -

PubMed ID

  • 27966532

Pubmed Central ID

  • PMC5171841

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms13666


  • eng

Conference Location

  • England