Genetic and epigenetic characteristics of gastric cancers with JC virus T-antigen

作     者：Satoshi Yamaoka Hiroyuki Yamamoto Katsuhiko Nosho Hiroaki Taniguchi Yasushi Adachi Shigeru Sasaki Yoshiaki Arimura Kohzoh Imai Yasuhisa Shinomura 

作者机构：First Department of Internal MedicineSapporo Medical UniversitySapporo 060-8543 Japan Sapporo Medical UniversitySapporo 060-8556 Japan 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2009年第15卷第44期

页      面：5579-5585页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：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) Grants-in-Aid for Cancer Research from the Ministry of Health,Laborand Welfare of Japan(Yamamoto H) 

主　　题：JC virus T-antigen Epstein-Barr virus Microsatellite instability Gastric cancer 

摘      要：AIM： To clarify the significance of JC virus （JCV） T-antigen （T-Ag） expression in human gastric cancer. METHODS： We investigated the relationship between TAg 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, K/MS, BRAF, PIK3CA genes were analyzed by 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. TAg positivity was not correlated with clinicopathological characteristics. TAg expression was detected in a similar percentage of EBV positive cancers （4 of 9, 44%） and EBV negative cancers （35 of 73, 48%）. TAg expression was detected in a significantly lower percentage of MSI-H cancers （14%） than in non MSI-H cancers （55%, P = 0.005）. TAg 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 TAg negative cancers （57%, P = 0.018）. TAg 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.