Discovery of novel hypermethylated genes in prostate cancer using genomic CpG island microarrays

PLoS One. 2009;4(3):e4830. doi: 10.1371/journal.pone.0004830. Epub 2009 Mar 13.


Background: Promoter and 5' end methylation regulation of tumour suppressor genes is a common feature of many cancers. Such occurrences often lead to the silencing of these key genes and thus they may contribute to the development of cancer, including prostate cancer.

Methodology/principal findings: In order to identify methylation changes in prostate cancer, we performed a genome-wide analysis of DNA methylation using Agilent human CpG island arrays. Using computational and gene-specific validation approaches we have identified a large number of potential epigenetic biomarkers of prostate cancer. Further validation of candidate genes on a separate cohort of low and high grade prostate cancers by quantitative MethyLight analysis has allowed us to confirm DNA hypermethylation of HOXD3 and BMP7, two genes that may play a role in the development of high grade tumours. We also show that promoter hypermethylation is responsible for downregulated expression of these genes in the DU-145 PCa cell line.

Conclusions/significance: This study identifies novel epigenetic biomarkers of prostate cancer and prostate cancer progression, and provides a global assessment of DNA methylation in prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology
  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • Bone Morphogenetic Protein 7 / genetics*
  • Cell Line, Tumor
  • CpG Islands
  • DNA Methylation / drug effects
  • DNA Methylation / genetics*
  • Decitabine
  • Down-Regulation
  • Epigenesis, Genetic
  • Gene Expression
  • Gene Silencing
  • Genes, Tumor Suppressor*
  • Genetic Markers
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • Oligonucleotide Array Sequence Analysis / methods
  • Prostatic Neoplasms / genetics*
  • Transcription Factors


  • Antimetabolites, Antineoplastic
  • BMP7 protein, human
  • Bone Morphogenetic Protein 7
  • Genetic Markers
  • Homeodomain Proteins
  • Transcription Factors
  • HOXA4 protein, human
  • Decitabine
  • Azacitidine