title: Epstein-Barr virus-associated gastric carcinoma.
abstract: Epstein-Barr virus (EBV) has been accepted as an infective agent causing gastric carcinoma (GC). EBV-associated GC, comprising nearly 10% of all cases of GC, is the monoclonal growth of EBV-infected epithelial cells, which express only several EBV-latent genes (Latency I program). Histopathologically, there are two subtypes, lymphoepithelioma-like carcinoma and the ordinary type of GC. Other features include the lace pattern of carcinoma cells in the intramucosal stage and the dense infiltration of lymphocytes and macrophages at the invasive site of the submucosa. The primary molecular abnormality in EBV-associated GC is global and non-random CpG island methylation in the promoter region of many cancer-related genes. Experimental studies have demonstrated that viral latent membrane protein 2A (LMP2A) is responsible for the promotion of DNA methylation. LMP2A up-regulates cellular DNMT1 through the phosphorylation of STAT3, resulting in the repression of tumor suppressor genes, such as PTEN, through promoter methylation. DNA methylation in EBV-infected stomach cells may be due to overdrive of the cellular defense against foreign DNA. Further studies on the mechanisms of epigenetic abnormalities will clarify the strategies for prevention and treatment of this particular type of GC with EBV infection.
authors.affiliation: Department of Pathology and Diagnostic Pathology, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan. mfukayama-tky@umin.ac.jp
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ushiku
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000821:virology*; D002277:Carcinoma / Q000235:genetics / Q000473:pathology / Q000821:virology*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000235:genetics / Q000473:pathology; D004854:Herpesvirus 4, Human / Q000302:isolation & purification / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology*; D015854:Up-Regulation; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C411744:DMAP1 protein, human; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D008565:Membrane Proteins; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014763:Viral Matrix Proteins; C446603:TPTE protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human