Genetic and epigenetic characteristics of gastric cancerswith JC virus T-antigen

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 EpsteinBarr 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.

Biomarker analysis in oesophagogastric cancer: Results from the REAL3 and TransMAGIC trials

“…The frequency of PIK3CA mutations identified here (2.5% in advanced disease, 5% in operable disease, most affecting exon 9), contrasts with a recent report of a 15.9% frequency in advanced gastric cancer, 83% of which were exon 20 mutations, 14 however, our results are more consistent with previously reported frequencies of 4-6.5%. [33][34][35][36] Loss of PTEN has been previously reported in up to 77% of gastric cancers, 16 but there is considerable variation in both the scoring and definition of null PTEN. In our study, loss of PTEN protein expression was detected in 15.0% of patients with advanced disease and 11.0% of those with operable disease.…”

Molecular Biology, Epidemiology, and Pathogenesis of Progressive Multifocal Leukoencephalopathy, the JC Virus-Induced Demyelinating Disease of the Human Brain

“…The JCV genome has also been reported for several tumors of nonneural origin, including colorectal cancer, gastric cancer, esophageal carcinoma, and lymphoma (65,69,111,116,131,132,157,193,261,280,282,340,350,365,417,447,449,450,513,549), although it should again be noted that there are also reports to the contrary (163,291,363). Consistent with observations in tumors of neural origin, examination of these tumor cells showed expression of T antigen, and in some cases agnoprotein, in tumor cells, where it was colocalized with p53 and ␤-catenin (65,111,116,131,261).…”

No Evidence for an Association between JC Polyomavirus Infection and Gastroduodenal Diseases

“…The expression of JCPyV LTag has been significantly associated with chromosomal instability in a colon cancer cell line [22]. In addition, expression of JCPyV LTag has been demonstrated in a subset of GC samples, and LTag-positive GCs showed a considerable increase in allelic losses and aberrant methylation [23,24]. Moreover, according to a recent study, the JCPyV DNA load was significantly higher in GCs than in normal gastric tissue [15].…”