1430 DEFINING THE FIELD DEFECT ASSOCIATED WITH PROSTATE CANCER DEVELOPMENT USING UNBIASED METHYLATION PROFILING (2010)

You have accessJournal of UrologyProstate Cancer: Basic Research VIII1 Apr 20101430 DEFINING THE FIELD DEFECT ASSOCIATED WITH PROSTATE CANCER DEVELOPMENT USING UNBIASED METHYLATION PROFILING Bing Yang, Jessica Kueck, Sachin Bhusari, Wei Huang, and David Jarrard Bing YangBing Yang More articles by this author , Jessica KueckJessica Kueck More articles by this author , Sachin BhusariSachin Bhusari More articles by this author , Wei HuangWei Huang More articles by this author , and David JarrardDavid Jarrard More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1123AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Many tumors, including age-related cancers like prostate cancer(PCa), are multifocal and surrounded by histologically normal appearing tissues containing molecular defects. DNA methylation, an epigenetic mechanism of gene regulation, is altered with aging and cancer. We hypothesized that defects in DNA methylation may occur as part of a field defect associated with PCa development. METHODS DNA methylation in 10 histologically normal tissues from men with and without cancer was compared in triplicate utilizing the Encode HG18 DNA methylation array (NimbleGen). This array contains 385,000 probes tiling biologically significant regions of the human genome. Methylation at significant sites(-log10(p) >10) was further assessed using bisulfite-based quantitative pyrosequencing in a separate group of samples (26), as well as 18 microdissected tissues consisting of a primary tumor, and tissues distant (near-2mm, far-10mm) from the primary. RESULTS We identified in prostate tissues containing associated cancer 31 hypomethylated and 12 hypermethylated probes significantly different from noncancer specimens(p < 0.01). Pyrosequencing on a separate sample pool (14 noncancer, 12 tumor-associated) confirmed these findings in 3/9 probes tested to date. Three probes were found to demonstrated altered methylation not only in the tumor, but also in near and far histologically normal tissues compared to noncancer samples confirming a field defect in prostate tissues containing cancer. DNA hypomethylation in probes associated with Mash2 (Achaete-scute complex homolog 2) and TP53BP1 (tumor protein P53 binding protein1) was confirmed and hypermethylation in MCF2L (cell line derived transforming sequence-like). Two probes were found to be cancer specific rather than associated with the field defect. Significant methylation differences ranged from 6-27% suggesting only a subset of cells within these tissues were altered. CONCLUSIONS A novel unbiased DNA methylation assay identified sites that differ between tumor-associated and normal prostate tissues marking a field of susceptibility associated with the development of prostate cancer. This field defect is not just adjacent to the tumor but widespread. These probes may be utilized as biomarkers for prostate cancer screening, have negative implications with regard to focal therapy, and provide clues regarding the biology of prostate cancer development. Madison, WI© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e551 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Bing Yang More articles by this author Jessica Kueck More articles by this author Sachin Bhusari More articles by this author Wei Huang More articles by this author David Jarrard More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...