title: Alu and Satα hypomethylation in Helicobacter pylori-infected gastric mucosae.
abstract: Global hypomethylation and regional hypermethylation are supposed to be hallmarks of cancer cells. During gastric carcinogenesis, in which Helicobacter pylori infection is causally involved, aberrant hypermethylation is already present in H. pylori-infected gastric mucosae. In contrast, little is known about global hypomethylation, which can be caused by hypomethylation of individual repetitive elements and other sequences. We, therefore, investigated hypomethylation of individual repetitive elements and the global 5-methylcytosine content in four groups of gastric mucosal samples that represented the time course of H. pylori infection and gastric carcinogenesis [gastric mucosae of H. pylori-negative healthy volunteers (G1, n = 34), H. pylori-positive healthy volunteers (G2, n = 42), H. pylori-positive gastric cancer patients (G3, n = 34) and H. pylori-negative gastric cancer patients (G4, n = 20)] and 52 primary gastric cancers. Major variants of Alu, LINE1 and Satα were identified, and their methylation levels were quantified by bisulfite pyrosequencing. Compared with G1, the Alu methylation level was decreased in G2, G3, G4 and cancers (89.2-97.1% of that in G1, p < 0.05). The Satα methylation level was decreased in G2 (91.6%, p < 0.05) and G3 (94.3%, p = 0.08) but not in G4 and cancers. The LINE1 methylation level was decreased only in cancers. The 5-methylcytosine content was at similar levels in G2, G3 and G4 and highly variable in cancers. These results showed that Alu and Satα hypomethylation is induced in gastric mucosae by H. pylori infection during gastric carcinogenesis, possibly in different target cells, and that global hypomethylation is not always present in human gastric cancers.
authors.affiliation: Carcinogenesis Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
authors.forename: Takeichi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamashita
authors.forename: Takeji
authors.initials: T
authors.lastname: Takamura-Enya
authors.forename: Tohru
authors.initials: T
authors.lastname: Niwa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ando
authors.forename: Shotaro
authors.initials: S
authors.lastname: Enomoto
authors.forename: Takao
authors.initials: T
authors.lastname: Maekita
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Nakazawa
authors.forename: Masae
authors.initials: M
authors.lastname: Tatematsu
authors.forename: Masao
authors.initials: M
authors.lastname: Ichinose
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Ushijima
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D020087:Alu Elements / Q000235:genetics*; D001483:Base Sequence; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D004276:DNA, Satellite / Q000235:genetics*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000382:microbiology / Q000503:physiopathology*; D016480:Helicobacter pylori / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; D004276:DNA, Satellite; D044503:5-Methylcytosine