Characterizing DNA methylation patterns in pancreatic cancer genome

Tan, Aik Choon; Jimeno, Antonio; Lin, Steven H.; Wheelhouse, Jenna; Chan, Fonda; Solomon, Anna; Rajeshkumar, N.V.; Rubio-Viqueira, Belen; Hidalgo, Manuel

doi:10.1016/j.molonc.2009.03.004

« Previous Next »Molecular Oncology
Volume 3, Issue 5 , Pages 425-438, December 2009

Characterizing DNA methylation patterns in pancreatic cancer genome

Aik Choon Tan
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine, Baltimore, MD, USA
Antonio Jimeno
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine, Baltimore, MD, USA
Steven H. Lin
- Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
Jenna Wheelhouse
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine, Baltimore, MD, USA
Fonda Chan
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine, Baltimore, MD, USA
Anna Solomon
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine, Baltimore, MD, USA
N.V. Rajeshkumar
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine, Baltimore, MD, USA
Belen Rubio-Viqueira
- Centro Integral Oncologico “Clara Campal”, Calle Oña, 10, 28050 Madrid, Spain
Manuel Hidalgo
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Centro Integral Oncologico “Clara Campal”, Calle Oña, 10, 28050 Madrid, Spain
- Correspondence to: Manuel Hidalgo, MD, PhD, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans St., Room 489, Baltimore, MD 21231, USA. Tel.: +1 410 5029746; fax: +1 410 6149006.

Received 3 February 2009; received in revised form 6 March 2009; accepted 9 March 2009. published online 08 May 2009.

Abstract

We performed a global methylation profiling assay on 1505 CpG sites across 807 genes to characterize DNA methylation patterns in pancreatic cancer genome. We found 289 CpG sites that were differentially methylated in normal pancreas, pancreatic tumors and cancer cell lines. We identified 23 and 35 candidate genes that are regulated by hypermethylation and hypomethylation in pancreatic cancer, respectively. We also identified candidate methylation markers that alter the expression of genes critical to gemcitabine susceptibility in pancreatic cancer. These results indicate that aberrant DNA methylation is a frequent epigenetic event in pancreatic cancer; and by using global methylation profiling assay, it is possible to identify these markers for diagnostic and therapeutic purposes in this disease.

Keywords: DNA methylation, Hypermethylation, Hypomethylation, Gene expression, Pancreatic cancer, Gemcitabine