Abstract 3210: Profiling of DNA methylation signature for different phases of prostate cancer development

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Prostate cancer is the third most common cancer in Singaporean men. Compared to Western countries, the prostate cancer incidence is lower in Asian countries but recent data suggest that incidence is increasing, especially in rapidly urbanized countries. Recent studies provide evidence that methylated genes can be useful and promising molecular biomarkers for detection of prostate cancers. The aim of our study is to identify a panel of global gene methylation signatures that are unique and specific for different phases of prostate cancer development and different prostate cancer phenotypes. This may thus differentiate cancers from non-cancers, and aggressive cancers from indolent ones. We have profiled methylation of genes using the Illumina's GoldenGate Methylation System. The Standard GoldenGate Methylation Cancer Panel I (Illumina Inc, San Diego, CA) spans 1,505 CpG loci selected from 807 genes that have been shown in literature to play important roles in cancer. Methylation levels of candidate genes were quantified in 28 benign tissues without prostate cancer, 52 tissues of Gleason score 3+3, 66 tissues of Gleason score 4+x and 37 tissues of Gleason score 5+x. DNA used for the assays were obtained from laser capture microdissected paraffin embedded archival tissues. Interestingly, our results showed that 28 different CpG loci were methylated in Gleason 3+3 prostate cancer tissues compared to benign prostatic hyperplasia tissues that were used as controls. In addition, methylation levels in prostate cancer samples of high Gleason index (4+x and 5+x) were significantly higher than the paired prostate cancer samples of low Gleason index (3+3) in at least 10 candidate genes. These genes include VIM (p-value 3.59E-08), ASCL2 (p-value 1.71E-09), DAB2IP (p-value 6.55E-08) and FRZB (p-value 6.44E-08). Together with bioinformatics and quantitative methylation-specific PCR, we identified a set of potentially phenotype-specific gene methylation signatures in Asian men. Our studies contributed to the improvement of diagnostic capability for prostate cancer beyond available tumour markers such as PSA as it is a more sensitive molecular correlate. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3210. doi:10.1158/1538-7445.AM2011-3210