Abstract 4999: Genome-wide methylation array of human prostate tissues using illumina infunium 450K bead chip reveals distinct DNA methylation signatures with potential as clinical predictors

Abstract

Prostate cancer (PCa) harbors a myriad of aberrant genomic and epigenetic alterations. Epigenetic inactivation of genes in PCa is largely based on transcriptional silencing by aberrant CpG methylation of CpG rich promoter regions. Candidate gene-based studies have identified a handful of aberrant CpG DNA methylation events in PCa. To better understand the role of aberrant epigenetic alterations and identify biological pathways likely to be affected by methylation mediated alterations in gene expression in PCa, we have examined the methylation status of 450,000 (450K) cytosine microarray (illumina). The 450K microarray includes CpG islands/shores/shelves/open sea, non-coding RNA and sites surrounding the transcription start sites for coding genes, but also for the corresponding gene bodies and the 3′-UTR. We demonstrate that the 450k DNA methylation array can significantly detect CpG methylation changes in radical prostatectomy prostate tissue samples. Cluster analysis revealed distinct DNA methylation profiles for prostate cancer tissues in comparison with non-malignant tissues. A total of 225 CpG loci (p > 0.00049) showed differential methylation in the cancer tissues in comparison with non-malignant tissues. Each of the 225 CpG locus was validated in silico using an independent, publicly available methylome dataset from the Cancer Genome Atlas. The majority of these loci were informative particularly in the prostate cancer. Overall, cluster analysis showed gene set enriched in pathways including transcriptional modifications, apoptosis/autophagy, chromatin assembly, growth factor signaling, cell cycle regulation and oxidative-redox reaction. This study shows that CpG locus methylation arrays could reveal important biological differences in the epigenome between prostate cancer and non-malignant tissues and provide potential markers for disease detection and/or progression.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4999. doi:1538-7445.AM2012-4999