Data from Genome-wide DNA Methylation Events in <i>TMPRSS2–ERG</i> Fusion-Negative Prostate Cancers Implicate an EZH2-Dependent Mechanism with <i>miR-26a</i> Hypermethylation

<div>Abstract<p>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 first 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 identified more than 147,000 cancer-associated epigenetic alterations. In addition, global methylation patterns show significant differences based on the <i>TMPRSS2–ERG</i> rearrangement status. We propose the hypermethylation of <i>miR-26a</i> as an alternative pathway of <i>ERG</i> rearrangement-independent <i>EZH2</i> activation. The observed increase in differential methylation events in fusion–negative tumors can explain the tumorigenic process in the absence of genomic rearrangements.</p><p><b>Significance:</b> In contrast to <i>TMPRSS2–ERG</i>-rearranged tumors, the pathomechanism for gene fusion–negative tumors is completely unclear. Using a sequencing-based approach, our work uncovers significant global epigenetic alterations in <i>TMPRSS2–ERG</i> gene fusion–negative tumors and provides a mechanistic explanation for the tumor formation process. <i>Cancer Discov; 2(11); 1024–35. ©2012 AACR</i>.</p><p>Read the Commentary on this article by Alumkal and Herman, p. 979.</p><p>This article is featured in Highlights of This Issue, p. 961</p></div>