Genome-wide analysis of promoter methylation associated with gene expression profile in pancreatic adenocarcinoma

Clin Cancer Res. 2011 Jul 1;17(13):4341-54. doi: 10.1158/1078-0432.CCR-10-3431. Epub 2011 May 24.


Purpose: The goal of this study was to comprehensively identify CpG island methylation alterations between pancreatic cancers and normal pancreata and their associated gene expression alterations.

Experimental design: We employed methylated CpG island amplification followed by CpG island microarray, a method previously validated for its accuracy and reproducibility, to analyze the methylation profile of 27,800 CpG islands covering 21 MB of the human genome in nine pairs of pancreatic cancer versus normal pancreatic epithelial tissues and in three matched pairs of pancreatic cancer versus lymphoid tissues from the same individual.

Results: This analysis identified 1,658 known loci that were commonly differentially methylated in pancreatic cancer compared with normal pancreas. By integrating the pancreatic DNA methylation status with the gene expression profiles of the same samples before and after treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine, and the histone deacetylase inhibitor, trichostatin A, we identified dozens of aberrantly methylated and differentially expressed genes in pancreatic cancers including a more comprehensive list of hypermethylated and silenced genes that have not been previously described as targets for aberrant methylation in cancer.

Conclusion: We expected that the identification of aberrantly hypermethylated and silenced genes will have diagnostic, prognostic, and therapeutic applications.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Cell Adhesion / genetics
  • Cell Line, Tumor
  • CpG Islands / genetics
  • DNA Methylation / genetics*
  • Epigenomics
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic*
  • Genetic Loci
  • Genome-Wide Association Study*
  • Humans
  • Multigene Family / genetics
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Pluripotent Stem Cells / metabolism
  • Promoter Regions, Genetic*
  • Signal Transduction / genetics
  • Wnt Proteins / metabolism


  • Wnt Proteins