A DNA methylation microarray-based study identifies ERG as a gene commonly methylated in prostate cancer

Jacob Schwartzman, Solange Mongoue-Tchokote, Angela Gibbs, Lina Gao, Christopher L. Corless, Jennifer Jin, Luai Zarour, Celestia Higano, Lawrence D. True, Robert L. Vessella, Beth Wilmot, Daniel Bottomly, Shannon K. McWeeney, Steven G. Bova, Alan W. Partin, Motomi Mori, Joshi J. Alumkal

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

DNA methylation of promoter regions is a common event in prostate cancer, one of the most common cancers in men worldwide. Because prior reports demonstrating that DNA methylation is important in prostate cancer studied a limited number of genes, we systematically quantified the DNA methylation status of 1,505 CpG dinucleotides for 807 genes in 78 paraffin-embedded prostate cancer samples and three normal prostate samples. The ERG gene, commonly repressed in prostate cells in the absence of an oncogenic fusion to the TMPRSS2 gene, was one of the most commonly methylated genes, occurring in 74% of prostate cancer specimens. In an independent group of patient samples, we confirmed that ERG DNA methylation was common, occurring in 57% of specimens, and cancer-specific. The ERG promoter is marked by repressive chromatin marks mediated by polycomb proteins in both normal prostate cells and prostate cancer cells, which may explain ERG's predisposition to DNA methylation and the fact that tumors with ERG DNA methylation were more methylated, in general. These results demonstrate that bead arrays offer a high-throughput method to discover novel genes with promoter DNA methylation such as ERG, whose measurement may improve our ability to more accurately detect prostate cancer.

Original languageEnglish (US)
Pages (from-to)1248-1256
Number of pages9
JournalEpigenetics
Volume6
Issue number10
DOIs
StatePublished - Oct 2011

Keywords

  • Biomarker
  • DNA methylation
  • ERG
  • Polycomb
  • Prostate cancer

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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