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

• Published in: World journal of gastroenterology : WJG 2009-11, Vol.15 (44), p.5579-5585
• Main Authors: Yamaoka, Satoshi, Yamamoto, Hiroyuki, Nosho, Katsuhiko, Taniguchi, Hiroaki, Adachi, Yasushi, Sasaki, Shigeru, Arimura, Yoshiaki, Imai, Kohzoh, Shinomura, Yasuhisa
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - immunology; Aged; Alleles; Antigens, Viral, Tumor - metabolism; Brief; Epigenesis, Genetic; Female; Humans; Immunohistochemistry - methods; JC Virus - metabolism; Loss of Heterozygosity; Male; Microsatellite Repeats - genetics; Middle Aged; Mutation; Sequence Analysis, DNA; Stomach Neoplasms - genetics; Stomach Neoplasms - immunology; 遗传特征
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.15.5579

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.