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| IJCEP Copyright © 2007-All rights reserved. |
| International Journal of Clinical and Experimental Pathology |
Int J Clin Exp Pathol 1(3):198-216;2008
Review Article
Epstein-Barr Virus and Gastric Carcinoma – Viral Carcinogenesis through Epigenetic
Mechanisms
Hiroshi Uozaki and Masashi Fukayama
Department of Pathology, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan
Received 13 Sept 2007; accepted and available online 1 January 2008
Abstract: Epstein-Barr virus (EBV)-associated gastric carcinoma (GC) is the monoclonal growth of EBV-infected epithelial cells, and the
entity was recognized only recently. EBV-associated GC is distributed worldwide and more than 90,000 patients are estimated to develop
GC annually in association with EBV (10% of total GC). EBV-associated GC occurs in two forms in terms of the histological features, i.e.,
lymphoepithelioma-like GC and ordinary type of GC. Both share characteristic clinicopathological features, such as the preferential
occurrence as multiple cancer and remnant stomach cancer. While the expression of EBV-latent genes is restricted to several in the
infected cells (Latency I), EBV-associated GC shows gastric cell phenotype, resistance to apoptosis, and the production of
immunomodulator molecules. Recently, global and non-random CpG island methylation of the promoter region of many cancer-related
genes has been demonstrated with their decreased expression, such as p16 INK4A, p73 and E-cadherin. This abnormality is
accompanied by methylation of the EBV genome itself, suggesting a process of virus-driven hypermethylation in the development of
neoplastic cells. Further studies are necessary to determine the precise sequence of EBV infection, methylation, transformation and
selection of the predominant clone within the stomach mucosa. Future studies are also desirable for the target and strategy of therapy,
such as initiating viral replication or reversing the DNA methylation of cellular genes. (IJCEP709007).
Key Words: Epstein-Barr virus, gastric cancer, DNA methylation, viral oncogenesis, histology, chronic inflammation
Full Text PDF
Address all correspondences to: Masashi Fukayama, M.D., Ph.D, Department of Pathology, Graduate School of Medicine, The University
of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan, Phone: +81-3-5841-3341, Fax: +81-3-3815-8379, Email: mfukayama-
tky@umin.ac.jp
Review Article
Epstein-Barr Virus and Gastric Carcinoma – Viral Carcinogenesis through Epigenetic
Mechanisms
Hiroshi Uozaki and Masashi Fukayama
Department of Pathology, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan
Received 13 Sept 2007; accepted and available online 1 January 2008
Abstract: Epstein-Barr virus (EBV)-associated gastric carcinoma (GC) is the monoclonal growth of EBV-infected epithelial cells, and the
entity was recognized only recently. EBV-associated GC is distributed worldwide and more than 90,000 patients are estimated to develop
GC annually in association with EBV (10% of total GC). EBV-associated GC occurs in two forms in terms of the histological features, i.e.,
lymphoepithelioma-like GC and ordinary type of GC. Both share characteristic clinicopathological features, such as the preferential
occurrence as multiple cancer and remnant stomach cancer. While the expression of EBV-latent genes is restricted to several in the
infected cells (Latency I), EBV-associated GC shows gastric cell phenotype, resistance to apoptosis, and the production of
immunomodulator molecules. Recently, global and non-random CpG island methylation of the promoter region of many cancer-related
genes has been demonstrated with their decreased expression, such as p16 INK4A, p73 and E-cadherin. This abnormality is
accompanied by methylation of the EBV genome itself, suggesting a process of virus-driven hypermethylation in the development of
neoplastic cells. Further studies are necessary to determine the precise sequence of EBV infection, methylation, transformation and
selection of the predominant clone within the stomach mucosa. Future studies are also desirable for the target and strategy of therapy,
such as initiating viral replication or reversing the DNA methylation of cellular genes. (IJCEP709007).
Key Words: Epstein-Barr virus, gastric cancer, DNA methylation, viral oncogenesis, histology, chronic inflammation
Full Text PDF
Address all correspondences to: Masashi Fukayama, M.D., Ph.D, Department of Pathology, Graduate School of Medicine, The University
of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan, Phone: +81-3-5841-3341, Fax: +81-3-3815-8379, Email: mfukayama-
tky@umin.ac.jp