title: Roles of Distal and Genic Methylation in the Development of Prostate Tumorigenesis Revealed by Genome-wide DNA Methylation Analysis.
abstract: Aberrant DNA methylation at promoters is often linked to tumorigenesis. But many aspects of DNA methylation remain unexplored, including the individual roles of distal and gene body methylation, as well as their collaborative roles with promoter methylation. Here we performed a MBD-seq analysis on prostate specimens classified into low, high, and very high risk group based on Gleason score and TNM stages. We identified gene sets with differential methylation regions (DMRs) in Distal, TSS, gene body and TES. To understand the collaborative roles, TSS was compared with the other three DMRs, resulted in 12 groups of genes with collaborative differential methylation patterns (CDMPs). We found several groups of genes that show opposite methylation patterns in Distal and Genic regions compared to TSS region, and in general they are differentially expressed genes (DEGs) in tumors in TCGA RNA-seq data. IPA (Ingenuity Pathway Analysis) reveals AR/TP53 signaling network to be a major signaling pathway, and survival analysis indicates genes subsets significantly associated with prostate cancer recurrence. Our results suggest that DNA methylation in Distal and Genic regions also plays critical roles in contributing to prostate tumorigenesis, and may act either positively or negatively with TSSs to alter gene regulation in tumors.
authors.affiliation: Department of Molecular Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, US.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Molecular Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, US.
authors.forename: Rohit Ramakant
authors.initials: RR
authors.lastname: Jadhav
authors.affiliation: Department of Molecular Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, US.
authors.forename: Joseph
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, US.
authors.forename: Desiree
authors.initials: D
authors.lastname: Wilson
authors.affiliation: Department of Epidemiology and Biostatistics, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, US.
authors.forename: Yidong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Urology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, US.|Cancer Therapy and Research Center, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, US.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Thompson
authors.affiliation: Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, US.
authors.forename: Dean A
authors.initials: DA
authors.lastname: Troyer
authors.affiliation: Department of Urology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, US.
authors.forename: Javier
authors.initials: J
authors.lastname: Hernandez
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Regents University, Augusta, GA 30912, US.
authors.forename: Huidong
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, US.|Department of Urology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, US.|Cancer Therapy and Research Center, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, US.
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Leach
authors.affiliation: Department of Molecular Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, US.|Cancer Therapy and Research Center, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, US.
authors.forename: Tim H-M
authors.initials: TH
authors.lastname: Huang
authors.affiliation: Department of Molecular Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, US.|Department of Epidemiology and Biostatistics, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, US.
authors.forename: Victor X
authors.initials: VX
authors.lastname: Jin
mesh_terms: D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D016019:Survival Analysis
chemical_list: D004273:DNA, Neoplasm