title: Comprehensive DNA Methylation Profiling of Inflammatory Mucosa in Ulcerative Colitis.
abstract: Aberrant DNA methylation frequently occurs in the inflammatory mucosa in ulcerative colitis (UC) and is involved in UC-related tumorigenesis. We performed comprehensive DNA methylation profiling of the promoter regions of the inflamed rectal mucosae of patients with UC.
  
  
  
  The methylation status of the promoter CpG islands (CGIs) of 45 cancer/inflammation or age-related candidate genes and the LINE1 repetitive element were examined in the colonic mucosae of 84 cancer-free patients with UC by bisulfite pyrosequencing. Methylation status of selected genes (DPYS, N33, MIR1247, GSTP1, and SOX11) was also determined in 14 neoplastic lesions (5 with high-grade dysplasia and 9 with carcinoma) and 8 adjacent tissues derived from 12 patients. An Infinium HumanMethylation450 BeadChip array was used to characterize the methylation status of >450,000 CpG sites for 10 patients with UC.
  
  
  
  Clustering analysis based on the methylation status of the candidate genes clearly distinguished the inflammatory samples from the noninflammatory samples. The hypermethylation of the promoter CGIs strongly correlated with increased disease duration, which is a known risk factor for the development of colon cancer. Genome-wide methylation analyses revealed a high rate of hypermethylation in the severe phenotype of UC, particularly at the CGIs. Exclusively hypermethylated promoter CGIs in the severe phenotypes were significantly related to genes involved in biosynthetic processes, the regulation of metabolic processes, and nitrogen compound metabolic processes.
  
  
  
  Our findings suggest the potential utility of DNA methylation as a molecular marker and therapeutic target for UC-related tumorigenesis.
authors.affiliation: *Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan; and †Department of Gastroenterology, Tanimukai Hospital Japan, Nishinomiya, Japan.
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Tahara
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hirata
authors.forename: Naoko
authors.initials: N
authors.lastname: Nakano
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Nagasaka
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shibata
authors.forename: Naoki
authors.initials: N
authors.lastname: Ohmiya
mesh_terms: D000328:Adult; D063646:Carcinogenesis / Q000235:genetics; D016000:Cluster Analysis; D003093:Colitis, Ulcerative / Q000150:complications / Q000235:genetics* / Q000473:pathology; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D007413:Intestinal Mucosa / Q000503:physiopathology*; D008297:Male; D010641:Phenotype; D012307:Risk Factors