No abstract

Prostate cancer is the second most common cancer among men worldwide. Alterations in the DNA methylation pattern can be one of the leading causes for prostate cancer formation. This study is the fi rst high-throughput sequencing study investigating genome-wide DNA methylation patterns in a large cohort of 51 tumor and 53 benign prostate samples using methylated DNA immunoprecipitation sequencing. Comparative analyses identifi ed more than 147,000 cancer-associated epigenetic alterations. In addition, global methylation patterns show signifi cant differences based on the TMPRSS2-ERG rearrangement status. We propose the hypermethylation of miR-26a as an alternative pathway of ERG rearrangement-independent EZH2 activation. The observed increase in differential methylation events in fusion-negative tumors can explain the tumorigenic process in the absence of genomic rearrangements. SIGNIFICANCE:In contrast to TMPRSS2-ERG -rearranged tumors, the pathomechanism for gene fusionnegative tumors is completely unclear. Using a sequencing-based approach, our work uncovers signifi cant global epigenetic alterations in TMPRSS2-ERG gene fusion-negative tumors and provides a mechanistic explanation for the tumor formation process. Cancer Discov; 2(11); 1024-35.