Abstract 164: High-throughput epigenetic analysis of susceptibility loci identified by GWAS in pancreatic cancer
| Autor: | Irene Collins, Rebecca R. Selzer, Robert Brazas, Hemang Parikh, H. Holster, Jinping Jia, Ken C. Lo, Laufey T. Amundadottir |
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| Rok vydání: | 2010 |
| Předmět: | |
| Zdroj: | Cancer Research. 70:164-164 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Pancreatic cancer is a highly lethal cancer with few well established risk factors. A genome wide association study (GWAS) of pancreatic cancer (PanScan) is being conducted within the framework of the NCI-sponsored Cohort Consortium and the Pancreatic Cancer Case-Control Consortium (PANC4). Susceptibility loci discovered to date in PanScan are non-coding variants that lie in intronic or intergenic regions, suggesting that the underlying signals may function through regulatory mechanisms that influence gene expression or splicing. Alternatively, these may lie in unannotated transcripts and directly affect their function. Epigenetic mechanisms, such as DNA methylation, can affect the regulation of gene expression and plays a critical role in the development of many human diseases including cancer. Powerful methods exist to analyze DNA methylation patterns in higher eukaryotes including methylated DNA immunoprecipitation (MeDIP), an affinity based approach to enrich methylated DNA regions from genomic DNA, which can be combined with microarrays to profile genomic DNA methylation patterns. We created a new semi-custom MeDIP-optimized array design based on our Human DNA Methylation 3×720K CpG Island Plus RefSeq Promoter array by tiling additional regions associated with pancreatic cancer that were identified in the PanScan study. To complement DNA methylation data a genome-wide transcriptome analysis was performed with RNA-sequencing (RNA-seq). Here we describe a comprehensive genome wide analysis of 8 pancreatic cancer cell lines to examine methylation patterns of Refseq promoters and annotated CpG islands as well as transcribed sequences. One of the susceptibility loci from PanScan is in the vicinity of the ABO gene on Chr9q34 where four SNPs (rs505922, rs495828, rs657152 and rs630014) are associated with a significantly increased risk of pancreatic cancer. As a pilot study, DNA methylation patterns and expressed sequences in this locus were investigated in cell lines derived from pancreatic tumors and normal pancreatic tissues. Our genome wide DNA methylation and RNA-seq analysis aims at establishing a comprehensive catalog of epigenetic patterns in pancreatic cell lines that could provide plausibility for the association signal in the ABO gene and other GWAS regions and thereby, initiate the characterization of the molecular phenotype of the susceptibility alleles for pancreatic cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 164. |
| Databáze: | OpenAIRE |
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