Brief Article
Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Nov 28, 2009; 15(44): 5579-5585
Published online Nov 28, 2009. doi: 10.3748/wjg.15.5579
Genetic and epigenetic characteristics of gastric cancers with JC virus T-antigen
Satoshi Yamaoka, Hiroyuki Yamamoto, Katsuhiko Nosho, Hiroaki Taniguchi, Yasushi Adachi, Shigeru Sasaki, Yoshiaki Arimura, Kohzoh Imai, Yasuhisa Shinomura
Satoshi Yamaoka, Hiroyuki Yamamoto, Katsuhiko Nosho, Hiroaki Taniguchi, Yasushi Adachi, Shigeru Sasaki, Yoshiaki Arimura, Yasuhisa Shinomura, First Department of Internal Medicine, Sapporo Medical University, Sapporo 060-8543, Japan
Kohzoh Imai, Sapporo Medical University, Sapporo 060-8556, Japan
Author contributions: Yamaoka S and Yamamoto H designed the research; Yamaoka S, Yamamoto H, Nosho K, Taniguchi H, Adachi Y and Sasaki S performed the research; Yamaoka S, Yamamoto H, Arimura Y, Imai K and Shinomura Y analyzed the data; Yamaoka S, Yamamoto H and Shinomura Y wrote the paper.
Supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Yamamoto H, Imai K and Shinomura Y) and Grants-in-Aid for Cancer Research from the Ministry of Health, Labor and Welfare of Japan (Yamamoto H)
Correspondence to: Hiroyuki Yamamoto, MD, FJSIM, PhD, First Department of Internal Medicine, Sapporo Medical University, S.-1, W.-16, Chuo-ku, Sapporo 060-8543, Japan. h-yama@sapmed.ac.jp
Telephone: +81-11-6112111 Fax: +81-11-6112282
Received: August 9, 2009
Revised: September 18, 2009
Accepted: September 25, 2009
Published online: November 28, 2009
Abstract

AIM: To clarify the significance of JC virus (JCV) T-antigen (T-Ag) expression in human gastric cancer.

METHODS: We investigated the relationship between T-Ag detected by immunohistochemistry and Epstein-Barr virus (EBV) infection, microsatellite instability (MSI), and genetic and epigenetic alterations in gastric cancers. Mutations in the p53, β-catenin, KRAS, BRAF, PIK3CA genes were analyzed by polymerase chain reaction (PCR)-single strand conformation polymorphism and DNA sequencing. Allelic losses were determined by PCR at 7 microsatellite loci. Aberrant DNA methylation was analyzed by MethyLight assay.

RESULTS: JCV T-Ag protein expression was found in 49% of 90 gastric cancer tissues. T-Ag positivity was not correlated with clinicopathological characteristics. T-Ag expression was detected in a similar percentage of EBV positive cancers (4 of 9, 44%) and EBV negative cancers (35 of 73, 48%). T-Ag expression was detected in a significantly lower percentage of MSI-H cancers (14%) than in non MSI-H cancers (55%, P = 0.005). T-Ag expression was detected in a significantly higher percentage of cancers with nuclear/cytoplasmic localization of β-catenin (15 of 21, 71%) than in cancers without (42%, P = 0.018). p53 mutations were detected in a significantly lower percentage of T-Ag positive cancers (32%) than in T-Ag negative cancers (57%, P = 0.018). T-Ag positive gastric cancers showed a significant increase in the allelic losses and aberrant methylation compared with T-Ag negative gastric cancers (P = 0.008 and P = 0.003).

CONCLUSION: The results suggest that JCV T-Ag is involved in gastric carcinogenesis through multiple mechanisms of genetic and epigenetic alterations.

Keywords: JC virus; T-antigen; Epstein-Barr virus; Microsatellite instability; Gastric cancer