title: Genome-wide DNA methylation profiles in noncancerous gastric mucosae with regard to Helicobacter pylori infection and the presence of gastric cancer.
abstract: OBJECTIVE
  To determine genome-wide DNA methylation profiles induced by Helicobacter pylori (H. pylori) infection and to identify methylation markers in H. pylori-induced gastric carcinogenesis.
  
  
  METHODS
  Gastric mucosae obtained from controls (n = 20) and patients with gastric cancer (n = 28) were included. A wide panel of CpG sites in cancer-related genes (1505 CpG sites in 807 genes) was analyzed using Illumina bead array technology. Validation of the results of Illumina bead array technique was performed using methylation-specific PCR method for four genes (MOS, DCC, CRK, and PTPN6).
  
  
  RESULTS
  The Illumina bead array showed that a total of 359 CpG sites (269 genes) were identified as differentially methylated by H. pylori infection (p < .0001). The correlation between methylation-specific PCR and bead array analysis was significant (p < .0001, Spearman coefficient = 0.5054). Methylation profiles in noncancerous gastric mucosae of the patients with gastric cancer showed quite distinct patterns according to the presence or absence of the current H. pylori infection; however, 10 CpG sites were identified to be hypermethylated and three hypomethylated in association with the presence of gastric cancer regardless of H. pylori infection (p < .01).
  
  
  CONCLUSIONS
  Genome-wide methylation profiles showed a number of genes differentially methylated by H. pylori infection. Methylation profiles in noncancerous gastric mucosae from the patients with gastric cancer can be affected by H. pylori-induced gastritis. Differentially methylated CpG sites in this study needs to be validated in a larger population using quantitative methylation-specific PCR method.
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea.
authors.forename: Cheol Min
authors.initials: CM
authors.lastname: Shin
authors.forename: Nayoung
authors.initials: N
authors.lastname: Kim
authors.forename: Younmu
authors.initials: Y
authors.lastname: Jung
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
authors.forename: Joo Sung
authors.initials: JS
authors.lastname: Kim
authors.forename: Hyun Chae
authors.initials: HC
authors.lastname: Jung
authors.forename: In Sung
authors.initials: IS
authors.lastname: Song
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism* / Q000382:microbiology; D016678:Genome; D016481:Helicobacter Infections / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology; D016480:Helicobacter pylori / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology