title: Identification of genes specifically methylated in Epstein-Barr virus-associated gastric carcinomas.
abstract: We studied the comprehensive DNA methylation status in the naturally derived gastric adenocarcinoma cell line SNU-719, which was infected with the Epstein-Barr virus (EBV) by methylated CpG island recovery on chip assay. To identify genes specifically methylated in EBV-associated gastric carcinomas (EBVaGC), we focused on seven genes, TP73, BLU, FSD1, BCL7A, MARK1, SCRN1, and NKX3.1, based on the results of methylated CpG island recovery on chip assay. We confirmed DNA methylation of the genes by methylation-specific PCR and bisulfite sequencing in SNU-719. The expression of the genes, except for BCL7A, was upregulated by a combination of 5-Aza-2'-deoxycytidine and trichostatin A treatment in SNU-719. After the treatment, unmethylated DNA became detectable in all seven genes by methylation-specific PCR. We verified DNA methylation of the genes in 75 primary gastric cancer tissues from 25 patients with EBVaGC and 50 EBV-negative patients who were controls. The methylation frequencies of TP73, BLU, FSD1, BCL7A, MARK1, SCRN1, and NKX3.1 were significantly higher in EBVaGC than in EBV-negative gastric carcinoma. We identified seven genes with promoter regions that were specifically methylated in EBVaGC. Inactivation of these genes may suppress their function as tumor suppressor genes or tumor-associated antigens and help to develop and maintain EBVaGC.
authors.affiliation: Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Okada
authors.forename: Munetaka
authors.initials: M
authors.lastname: Nakamura
authors.forename: Jun
authors.initials: J
authors.lastname: Nishikawa
authors.forename: Kouhei
authors.initials: K
authors.lastname: Sakai
authors.forename: Yibo
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mari
authors.initials: M
authors.lastname: Saito
authors.forename: Akihiro
authors.initials: A
authors.lastname: Morishige
authors.forename: Atsunori
authors.initials: A
authors.lastname: Oga
authors.forename: Kosuke
authors.initials: K
authors.lastname: Sasaki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suehiro
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hinoda
authors.forename: Isao
authors.initials: I
authors.lastname: Sakaida
mesh_terms: D000368:Aged; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002277:Carcinoma / Q000235:genetics* / Q000821:virology; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000737:chemistry* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D000077209:Decitabine; D020031:Epstein-Barr Virus Infections / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000821:virology; D014157:Transcription Factors / Q000235:genetics; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C098982:BCL7A protein, human; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C429034:FSD1 protein, human; D018398:Homeodomain Proteins; D006877:Hydroxamic Acids; D008840:Microfilament Proteins; C491178:NKX3-1 protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C471696:SCRN1 protein, human; C000606460:TP73 protein, human; D014157:Transcription Factors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C472720:ZMYND10 protein, human; C012589:trichostatin A; D000077209:Decitabine; C105547:MARK1 protein, human; D017346:Protein Serine-Threonine Kinases; D001374:Azacitidine