title: Epigenomic profiling of DNA methylation in paired prostate cancer versus adjacent benign tissue.
abstract: BACKGROUND
  Aberrant DNA methylation may promote prostate carcinogenesis. We investigated epigenome-wide DNA methylation profiles in prostate cancer (PCa) compared to adjacent benign tissue to identify differentially methylated CpG sites.
  
  
  METHODS
  The study included paired PCa and adjacent benign tissue samples from 20 radical prostatectomy patients. Epigenetic profiling was done using the Infinium HumanMethylation450 BeadChip. Linear models that accounted for the paired study design and False Discovery Rate Q-values were used to evaluate differential CpG methylation. mRNA expression levels of the genes with the most differentially methylated CpG sites were analyzed.
  
  
  RESULTS
  In total, 2,040 differentially methylated CpG sites were identified in PCa versus adjacent benign tissue (Q-value < 0.001), the majority of which were hypermethylated (n = 1,946; 95%). DNA methylation profiles accurately distinguished between PCa and benign tissue samples. Twenty-seven top-ranked hypermethylated CpGs had a mean methylation difference of at least 40% between tissue types, which included 25 CpGs in 17 genes. Furthermore, for 10 genes over 50% of promoter region CpGs were hypermethylated in PCa versus benign tissue. The top-ranked differentially methylated genes included three genes that were associated with both promoter hypermethylation and reduced gene expression: SCGB3A1, HIF3A, and AOX1. Analysis of The Cancer Genome Atlas (TCGA) data provided confirmatory evidence for our findings.
  
  
  CONCLUSIONS
  This study of PCa versus adjacent benign tissue showed many differentially methylated CpGs and regions in and outside gene promoter regions, which may potentially be used for the development of future epigenetic-based diagnostic tests or as therapeutic targets.
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.|Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.
authors.forename: Milan S
authors.initials: MS
authors.lastname: Geybels
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.|National Institute of Environmental Health Sciences, Biostatistics and Computational Biology Branch, Research Triangle Park, North Carolina.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Chao-Jen
authors.initials: CJ
authors.lastname: Wong
authors.affiliation: Illumina, Inc., San Diego, California.
authors.forename: Marina
authors.initials: M
authors.lastname: Bibikova
authors.affiliation: Illumina, Inc., San Diego, California.
authors.forename: Brandy
authors.initials: B
authors.lastname: Klotzle
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Michael
authors.initials: M
authors.lastname: Wu
authors.affiliation: Cancer Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland.
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Ostrander
authors.affiliation: Illumina, Inc., San Diego, California.
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Fan
authors.affiliation: MD Anderson Cancer Center, Houston, Texas.
authors.forename: Ziding
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.|Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington.
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stanford
mesh_terms: D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
keywords: DNA methylation; benign; mRNA expression; prostate cancer; tumor