Genetic and epigenetic characteristics of gastric cancers with JC virus T-antigen.
OBJECTIVE
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, beta-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 beta-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).


CONCLUSIONS
The results suggest that JCV T-Ag is involved in gastric carcinogenesis through multiple mechanisms of genetic and epigenetic alterations.
Yamaoka
Satoshi
S
First Department of Internal Medicine, Sapporo Medical University, Chuo-ku, Sapporo, Japan.
Yamamoto
Hiroyuki
H
Nosho
Katsuhiko
K
Taniguchi
Hiroaki
H
Adachi
Yasushi
Y
Sasaki
Shigeru
S
Arimura
Yoshiaki
Y
Imai
Kohzoh
K
Shinomura
Yasuhisa
Y
D000230:Adenocarcinoma / Q000235:genetics* / Q000276:immunology*; D000368:Aged; D000483:Alleles; D000957:Antigens, Viral, Tumor / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007577:JC Virus / Q000378:metabolism*; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000235:genetics* / Q000276:immunology*
D000957:Antigens, Viral, Tumor