Abstract 167: Identification of differentially methylated genes in normal prostate tissues from African American and Caucasian men

Abstract

Abstract BACKGROUND. Prostate cancer (PCa) is a common malignancy and a leading cause of cancer deaths among men in the United States. African American men have both a higher incidence and significantly higher mortality rates than Caucasian men. Abundant evidence has accumulated to suggest that epigenetic DNA methylation changes may appear earlier during PCa development than genetic changes, as well as more commonly and consistently. Most studies have emphasized DNA hypermethylation as an important mechanism for inactivation of key regulatory genes in prostate cancers. Thus methylated genes can serve as biomarkers for the detection of cancer from clinical specimens such as tissue biopsies or body fluids. However, very few studies have investigated differences in DNA methylation pattern in different ethnic groups or their application as ethnic sensitive biomarkers for disease detection. We hypothesize that differential methylation patterns maybe associated with ethnicity and could potentially contribute to the incidence and mortality of prostate cancer. METHODS. We have identified several genes to be differentially methylated in human prostate cancer cell line using methylated CpG island amplification coupled with CpG promoter microarray. Pyrosequencing was used to quantitatively measure the methylation levels of CDH11, FOXN4, PAX9, TIMP3, RPRM, SPARC, TCF3,CYP27B1, RARβ2, AR, GSTP1, NKX2-5, RASSF1A and TIMP3 genes in prostate cell lines, matched pairs of benign and prostate cancer tissues from individual prostate cancer patients, and normal prostate biopsies from African American and Caucasian men. Real time PCR was used to determine gene expression at the RNA transcript level. RESULTS. DNA hypermethylation was observed for NKX2-5, FOXN4, TIMP3, RPRM, TCF, SPARC, GSTP1, RASSF1A, RARβ2 and SPARC in prostate cancer cells and prostate cancer tissues samples. Higher frequency of methylation was observed for several genes including NKX2-5, GSTP1, RASSF1A, and RARβ2 genes in punch biopsies of normal prostate samples obtained from African American men in comparison to samples from Caucasian men. CONCLUSION. Our observations suggest a genome wide differential methylation patterns in prostate tissue samples obtained from African American men versus Caucasian men. Such alterations could account for some of the biological differences underlying prostate cancer disparity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 167.