Abstract #4744: Global histone modification and genome-wide methylation profiling reveals distinct epigenetic signatures in human prostate cancer

Aberrant epigenetic changes involving both histone modifications and DNA methylation have been observed in prostate cancer and identified as potential biomarkers as well as a key mechanism in carcinogenesis. Recent advances in molecular measurement technologies have allowed for high throughput analysis of epigenetic profiling by measuring genome-wide localization of histone modifications and DNA methylation. In the present study, we applied customized reverse-phase protein microarrays (RPA) to quantify the global histone modification abundance in addition to a genome-wide array platform measuring DNA methylation to study the global epigenetic profile of human prostate cancer. The samples analyzed were eight ethanol-fixed, paraffin-embedded clinical prostate specimens dissected into normal and cancer regions. Four additional snap frozen prostate cases are also included for further confirmation of the data. From a subset of these clinical prostate cases, DNA was extracted from the same dissected normal and tumor regions, and its methylation profile was evaluated using a bisulfite-modified-DNA cytosine genotyping array platform. Using commercially available, modification-specific antibodies, we analyzed acetylation, phosphorylation, and mono-, di- and tri-methylation on various histone N-terminal amino acids in matched normal and tumor regions from human prostate specimens. Unsupervised hierarchical clustering analysis was done by using a total of 24 histone modification targets, and suggests that normal and tumor samples tend to cluster group by patient. In contrast, DNA methylation analysis of 1505 CpG targets revealed > 100 targets that manifest uniform differential methylation between normal and tumor sample groups. Overall, the results provide a combined large-scale epigenetic screening including both the histone code and DNA methylation analysis of clinical samples, and offers new insights into the global epigenetic profile of human prostate cancer. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4744.