Detection of JC virus DNA sequences in colorectal cancers in Japan

Abstract

JC virus (JCV), a ubiquitous polyoma virus that commonly infects humans, was first identified as the etiologic agent for the fetal demyelinating disease, progressive multifocal leukoencephalopathy. Recently, a number of reports have documented detection of JCV in samples derived from several types of neural as well as non-neural human tumors. It has been suggested that oncogenicity of JCV depends on a T antigen having a strict structural homology to the T antigen of simian virus 40. To clarify whether JCV might have a potential role with regard to colorectal cancers, we investigated the presence of its genome in a series of cases along with colorectal adenomas and normal colonic mucosa, targeting T antigen, VP and agnoprotein by nested polymerase chain reaction and Southern blotting and T antigen by immunohistochemistry. While VP and agnoprotein were not found in any of the samples examined, T antigen was detected in 6 of 23 colorectal cancers (26.1%) and 1 of 21 adenomas (4.8%), but none of 20 samples of normal colonic mucosa. No clear and diffuse staining with anti-T-antigen antibodies (1:100) could be detected, and there was no correlation with CD20-positive cells, which might have indicated JCV latent infection of B lymphocytes. Presence of T antigen did not influence clinicopathological variables, including survival. In one colonic cancer case positive for T antigen together with lymph node metastasis, DNA extracted from cancer cells in the lymph node revealed no detection of T antigen. Our results are in the intermediate position between the high T antigen rate (81%) in one report and the lack of it (0%) in another focused on colon cancers. It was concluded that T antigen might be integrated in cancer cells in approximately one fourth of Japanese colon cancer cases without clear and diffuse expression of the protein, suggesting a possible role in oncogenesis which might involve a hit-and-run mechanism.

JC virus existence in Chinese gastrointestinal carcinomas

“…In our previous study, it was found that JCV T antigen existence or copies were closely linked to the lung, tongue, pharyngeal and gastric carcinogenesis (10,14,15,20). Hori et al (9) reported that T antigen was detected in 6 of 23 colorectal cancer cases (26.1%) and 1 of 21 adenomas (4.8%), but none of the 20 samples of normal colonic mucosa. These findings indicated that JCV T antigen may be involved in the malignant transformation of epithelium as evidenced by our transgenic lens tumor induced by T antigen, although we failed to establish the animal model of gastric tumor induced by the JCV T antigen (28).…”

The Role of Infectious Agents in Colorectal Carcinogenesis

“…Ten studies, with sample sizes ranging from 18 to 186, detected JCV genomic sequences in 9-89% of colorectal carcinomas and 5-82% of adenomatous tissue (Laghi et al, 1999;Theodoropoulos et al, 2005; R. Hori et al, 2005;Casini et al, 2005;Enam et al, 2002;Goel et al, 2006;P. Y. Lin et al, 2008, Niv et al, 2010aKarpinski et al, 2011;Jung et al, 2008).…”

The immune response to sporadic colorectal cancer in a novel mouse model

“…The contribution of Tag of JC polyomavirus to human colon carcinogenesis was investigated in several studies with controversial results (Newcomb et al, 2004;Hori et al, 2005;Weinreb, 2006). Vil-Cre  LoxP-Tag mice allowed the analysis of Taginduced tumorigenesis in the colon, which, however, was hampered by tumors in the thymus and Tag-specific CTL tolerance.…”