Differential DNA methylation patterns in normal and neoplastic pancreatic tissues and associated effects on gene expression

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NCI	EPIGEN/TRANS/CHROM-4

Authors

• J Hoskins
• J Jinping
• H Parikh
• I Collins
• K Lo
• S Hussain
• L Amundadottir

Abstract

Pancreatic cancer ranks among the most deadly cancers, with a mortality rate nearly equal to its rate of incidence. Previous works have reported significantly different DNA methylation profiles between tumor and normal pancreatic samples across the genome, suggesting epigenetic effects on gene expression. In this study we have used a customized NimbleGen 720K CpG Island Plus RefSeq Promoter Array in methyl-DNA immunoprecipitation (MeDIP) analysis of 10 pancreatic cell lines (1 normal and 9 tumor derived) and 10 paired normal/tumor tissue samples. By using a “Probe Sliding Window” ANOVA analysis, we found 29,765 peaks of significant (FDR corrected p<0.01) differential methylation between tumor-derived cell lines and normal pancreatic tissue, which were potentially associated with 17,167 genes (8805 hypermethylated, 8362 hypomethylated in tumor cells). Previous studies have reported less than 2000 differentially methylated genes in pancreatic tumor samples, and our results are in agreement with over half of these genes. Many differentially methylated genes showed gene expression changes consistent with their epigenetic modification, including several that are at or near loci associated with pancreatic cancer risk in GWA studies. Further analysis of this data should yield new information on DNA methylation changes in pancreatic cancer, and their effects on gene expression.

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