PURPOSE: To assess differentially methylated 'landscapes' according to prostate cancer (PCa) Gleason score (GS) and ERG oncogene expression status, and to determine the extent of polycomb group (PcG) target gene involvement, we sought to assess the genome-wide DNA methylation profile of PCa according to GS and ERG expression.
EXPERIMENTAL DESIGN: Genomic DNA from 39 PCa specimens was hybridized to CpG island microarrays through differential methylation hybridization. We compared methylation profiles between GS and ERG expression status as well as GS stratified by ERG expression status. In addition, we compared results from our dataset to publicly available datasets of histone modifications in benign prostate cells.
RESULTS: We discovered hundreds of distinct differentially methylated regions (DMRs) associated with increasing GS and ERG. Furthermore, the number of DMRs associated with GS was greatly expanded by stratifying samples into ERG positive versus ERG negative, with ERG positive/GS associated DMRs being primarily hypermethylated as opposed to hypomethylated. Finally, we found that there was a significant overlap between either GS-related or ERG hypermethylated DMRs and distinct regions in benign epithelial cells that have PcG signatures (H3K27me3, SUZ12) and lack active gene expression signatures (H3K4me3, RNA pol II).
CONCLUSIONS: This work defines methylation landscapes of PCa according to GS, and suggests that initiating genetic events may influence the PCa epigenome which is further perturbed as PCa progresses. Moreover, CpG islands with silent chromatin signatures in benign cells are particularly susceptible to PCa related hypermethylation.
Written by:
Kron K, Trudel D, Pethe V, Briollais L, Fleshner N, van der Kwast T, Bapat B. Are you the author?
Laboratory Medicine and Pathobiology, University of Toronto.
Reference: Clin Cancer Res. 2013 Apr 2. Epub ahead of print.
doi: 10.1158/1078-0432.CCR-12-3139
PubMed Abstract
PMID: 23549870
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