title: Methylome-wide Sequencing Detects DNA Hypermethylation Distinguishing Indolent from Aggressive Prostate Cancer.
abstract: A critical need in understanding the biology of prostate cancer is characterizing the molecular differences between indolent and aggressive cases. Because DNA methylation can capture the regulatory state of tumors, we analyzed differential methylation patterns genome-wide among benign prostatic tissue and low-grade and high-grade prostate cancer and found extensive, focal hypermethylation regions unique to high-grade disease. These hypermethylation regions occurred not only in the promoters of genes but also in gene bodies and at intergenic regions that are enriched for DNA-protein binding sites. Integration with existing RNA-sequencing (RNA-seq) and survival data revealed regions where DNA methylation correlates with reduced gene expression associated with poor outcome. Regions specific to aggressive disease are proximal to genes with distinct functions from regions shared by indolent and aggressive disease. Our compendium of methylation changes reveals crucial molecular distinctions between indolent and aggressive prostate cancer.
authors.affiliation: Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195, USA; Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Bhasin
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Byron H
authors.initials: BH
authors.lastname: Lee
authors.affiliation: Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Lars
authors.initials: L
authors.lastname: Matkin
authors.affiliation: Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Margaret G
authors.initials: MG
authors.lastname: Taylor
authors.affiliation: Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN 37240, USA.
authors.forename: Yaomin
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Magi-Galluzzi
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Klein
authors.affiliation: Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195, USA; Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA. Electronic address: tinga@ccf.org.
authors.forename: Angela H
authors.initials: AH
authors.lastname: Ting
mesh_terms: D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D021901:DNA, Intergenic / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D025341:Principal Component Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D021901:DNA, Intergenic