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Metadata

Name
ICGC Pancreas: Genomewide DNA methylation patterns in pancreatic ductal adenocarcinoma (gene expression of 103 samples)
Repository
Gemma
Identifier
gemma.experiment:8660
Description
Epigenetic modifications, particularly DNA methylation have been increasingly implicated in cancer. Although some genes display aberrant methylation in pancreatic cancer, a comprehensive global analysis is yet to be performed. To define the genome-wide pattern of DNA methylation in pancreatic ductal adenocarcinomas (PDAC), the methylation profile of 156 PDAC and 23 non-malignant pancreas was captured using high-density arrays. More than 90,000 CpG sites were significantly differentially methylated (DM) in PDAC relative to non-malignant pancreas, with pronounced alterations in a sub-set of 13,517 CpG sites. This sub-set of differentially methylated CpG sites segregated PDAC from non-malignant pancreas, regardless of tumour cellularity. As expected, PDAC hyper-methylation was most prevalent in the 5’ region of genes (including the proximal promoter, 5’UTR and CpG islands). From 3981 genes aberrantly methylated, approximately 36% showed significant correlation between methylation and mRNA expression levels. Pathway analysis revealed an enrichment of aberrant methylation in genes involved in key molecular mechanisms important to PDAC: TGF-?, WNT, Integrin signaling, Cell adhesion, Stellate cell activation and Axon guidance. Bisulfite amplicon deep sequencing and qRT-PCR expression analyses of axon guidance pathway genes SLIT2, SLIT3, ROBO1, ROBO3, SRGAP1, and MET suggested epigenetic suppression of SLIT-ROBO signaling and up-regulation of MET expression. Hypo-methylation of MET and ITGA2 correlated with high gene expression, which correlated with poor survival of PDAC patients. These data suggest that aberrant methylation plays an important role in pancreatic carcinogenesis affecting known core signaling pathways with important implications for disease pathophysiology and therapy. This dataset includes gene expression data from 103 primary tumour samples. 86 samples from this dataset have already been deposited into GEO (GSE36924), and has been duplicated here since the data has been processed differently. This data is also available through the International Cancer Genome Consortium (ICGC) Data Portal (http://dcc/icgc.org), under the project code: Pancreatic Cancer (QCMG, AU). Access to the restricted clinical data must be made through the ICGC Data Access Compliance Office (http://www.icgc.org/daco).
Last Updated (by provider): May 05 2014
Contributors: Suzanne Manning David Wood Conrad Leonard Katia Nones Sean M Grimmond Ann-Marie Patch Mark J Cowley Rita T Lawlor Angelika Christ Sarah Song Mark Pinese Darrin Taylor Jianmin Wu John V Pearson Karin S Kassahn Andrew V Biankin David K Chang Ilse Rooman Marina Pajic Nic Waddell David Miller Marc Jones Michelle Thomas Amber Johns Clare Watson Anthony J Gill Aldo Scarpa Craig Nourse Peter Bailey
Data or Study Types
gene expression
Keywords
functional genomics
Source Organization
University of British Columbia
Access Conditions
available
Access Hyperlink
www.chibi.ubc.ca/Gemma/expressionExperiment/showExpressionExperiment.html?id=8660

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