{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T06:52:32Z","timestamp":1759042352837},"reference-count":62,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2010,11,23]],"date-time":"2010-11-23T00:00:00Z","timestamp":1290470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Health Research Board and the Irish Cancer Society"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2011,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Aberrant DNA methylation has been implicated as a key survival mechanism in cancer, whereby promoter hypermethylation silences genes essential for many cellular processes including apoptosis. Limited data is available on the methylation profile of apoptotic genes in prostate cancer (CaP). The aim of this study was to profile methylation of apoptotic\u2010related genes in CaP using denaturing high performance liquid chromatography (DHPLC).<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Based on an in silico selection process, 13 genes were screened for methylation in CaP cell lines using DHPLC. Quantitative methylation specific PCR was employed to determine methylation levels in prostate tissue specimens (n\u2009=\u2009135), representing tumor, histologically benign prostate, high\u2010grade prostatic intraepithelial neoplasia and benign prostatic hyperplasia. Gene expression was measured by QRT\u2010PCR in cell lines and tissue specimens.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>The promoters of<jats:italic>BIK<\/jats:italic>,<jats:italic>BNIP3<\/jats:italic>,<jats:italic>cFLIP<\/jats:italic>,<jats:italic>TMS1<\/jats:italic>,<jats:italic>DCR1<\/jats:italic>,<jats:italic>DCR2<\/jats:italic>, and<jats:italic>CDKN2A<\/jats:italic>appeared fully or partially methylated in a number of malignant cell lines. This is the first report of aberrant methylation of<jats:italic>BIK<\/jats:italic>,<jats:italic>BNIP3<\/jats:italic>, and<jats:italic>cFLIP<\/jats:italic>in CaP. Quantitative methylation analysis in prostate tissues identified 5 genes (<jats:italic>BNIP3<\/jats:italic>,<jats:italic>CDKN2A<\/jats:italic>,<jats:italic>DCR1<\/jats:italic>,<jats:italic>DCR2<\/jats:italic>and<jats:italic>TMS1<\/jats:italic>) which were frequently methylated in tumors but were unmethylated in 100% of benign tissues. Furthermore, 69% of tumors were methylated in at least one of the five\u2010gene panel. In the case of all genes, except<jats:italic>BNIP3<\/jats:italic>, promoter hypermethylation was associated with concurrent downregulation of gene expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>Future examination of this \u201cCaP apoptotic methylation signature\u201d in a larger cohort of patients is justified to further evaluate its value as a diagnostic and prognostic marker. Prostate 71: 1\u20137, 2011. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.21212","type":"journal-article","created":{"date-parts":[[2010,6,16]],"date-time":"2010-06-16T13:13:37Z","timestamp":1276694017000},"page":"1-17","source":"Crossref","is-referenced-by-count":16,"title":["In silico analysis and DHPLC screening strategy identifies novel apoptotic gene targets of aberrant promoter hypermethylation in prostate cancer"],"prefix":"10.1002","volume":"71","author":[{"given":"Therese 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