Unmasking risk loci: DNA methylation illuminates the biology of cancer predisposition: Analyzing DNA methylation of transcriptional enhancers reveals missed regulatory links between cancer risk loci and genes

Dvir Aran, Asaf Hellman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Paradoxically, DNA sequence polymorphisms in cancer risk loci rarely correlate with the expression of cancer genes. Therefore, the molecular mechanism underlying an individual's susceptibility to cancer has remained largely unknown. However, recent evaluations of the correlations between DNA methylation and gene expression levels across healthy and cancerous genomes have revealed enrichment of disease-related DNA methylation variations within disease-associated risk loci. Moreover, it appears that transcriptional enhancers embedded in cancer risk loci often contain DNA methylation sites that closely define the expression of prominent cancer genes, despite the lack of significant correlations between gene expression levels and the surrounding disease-associated polymorphic sequences. We suggest that DNA methylation variations may obscure the effect of co-residing risk sequence alleles. Analysis of enhancer methylation data may help to reveal the regulatory circuits underlying predisposition to cancers and other common diseases. Editor's suggested further reading in BioEssays DNA methylation reprogramming in cancer: Does it act by re-configuring the binding landscape of Polycomb repressive complexes?

Original languageAmerican English
Pages (from-to)184-190
Number of pages7
JournalBioEssays
Volume36
Issue number2
DOIs
StatePublished - Feb 2014

Keywords

  • Cancer
  • Common human disease
  • DNA methylation
  • Disease risk loci
  • Epigenomics
  • Gene regulation
  • Transcriptional enhancers

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