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.
Similar content being viewed by others
References
Agostini HT, Yanagihara R, Davis V, Ryschkewitsch CF, Stoner GL (1997) Asian genotypes of JC virus in native Americans and in a Pacific Island population: markers of viral evolution and human migration. Proc Natl Acad Sci U S A 94:14542–14546
Agostini HT, Jobes DV, Stoner GL (2001) In: Khalili K, Stoner GD (eds) Molecular evolution and epidemiology of JC virus: molecular and clinical perspectives. Wiley-Liss, New York, pp 491–526
Bofill-Mas S, Formiga-Cruz M, Clemente-Casares P, Calafell F, Girones R (2001) Potential transmission of human polyomaviruses through the gastrointestinal tract after exposure to virions or viral DNA. J Virol 75:10290–10299
Chesters PM, Heritage J, McCance DJ (1983) Persistence of DNA sequences of BK virus and JC virus in normal human tissues and in diseased tissues. J Infect Dis 147:676–684
Dean FB, Bullock P, Murakami Y, Wobbe CR, Weissbach L, Hurwitz J (1987) Simian virus 40 (SV40) DNA replication: SV40 large T antigen unwinds DNA containing the SV40 origin of replication. Proc Natl Acad Sci U S A 84:16–20
Del Valle L, Delbue S, Gordon J, Enam S, Croul S, Ferrante P, Khalili K (2002) Expression of JC virus T-antigen in a patient with MS and glioblastoma multiforme. Neurology 58:895–900
Del Valle L, Gordon J, Enam S, Delbue S, Croul S, Abraham S, Radhakrishnan S, Assimakopoulou M, Katsetos CD, Khalili K (2002) Expression of human neurotropic polyomavirus JCV late gene product agnoprotein in human medulloblastoma. J Natl Cancer Inst 94:267–273
Dornreiter I, Hoss A, Arthur AK, Fanning E (1990) SV40 T antigen binds directly to the large subunit of purified DNA polymerase alpha. EMBO J 9:3329–3336
Enam S, Del Valle L, Lara C, Gan DD, Ortiz-Hidalgo C, Palazzo JP, Khalili K (2002) Association of human polyomavirus JCV with colon cancer: evidence for interaction of viral T-antigen and beta-catenin. Cancer Res 62:7093–7101
Gan DD, Reiss K, Carrill T, Del Valle L, Croul S, Giordano A, Fishman P, Khalili K (2001) Involvement of Wnt signaling pathway in murine medulloblastoma induced by human neurotropic JC virus. Oncogene 20:4864–4870
Hara H, Kaji H (1987) Random integration of SV40 in SV40-transformed, immortalized human fibroblasts. Exp Cell Res 168:531–538
Ikegaya H, Iwase H (2004) Trial for the geographical identification using JC viral genotyping in Japan. Forensic Sci Int 139:169–172
Imperiale M (2001) In: Khalili K, Stoner GL (eds) The human polyoma viruses: molecular and clinical perspective. Wiley-Liss, New York, pp 53–71
Inoue T, Nabeshima K, Kataoka H, Koono M (1996) Feasibility of archival non-buffered formalin-fixed and paraffin-embedded tissues for PCR amplification: an analysis of resected gastric carcinoma. Pathol Int 46:997–1004
Jeong BH, Lee KH, Choi EK, Kim K, Kim YS (2004) Genotyping of the JC virus in urine samples of healthy Korean individuals. J Med Virol 72:281–289
Khalili K, Del Valle L, Otte J, Weaver M, Gordon J (2003) Human neurotropic polyomavirus, JCV, and its role in carcinogenesis. Oncogene 22:5181–5191
Krynska B, Gordon J, Otte J, Franks R, Knobler R, DeLuca A, Giordano A, Khalili K (1997) Role of cell cycle regulators in tumor formation in transgenic mice expressing the human neurotropic virus, JCV, early protein. J Cell Biochem 67:223–230
Mandl CW, Frisque RJ (1986) Characterization of cells transformed by the human polyomavirus JC virus. J Gen Virol 67(Pt 8):1733–1739
Melendy T, Stillman B (1993) An interaction between replication protein A and SV40 T antigen appears essential for primosome assembly during SV40 DNA replication. J Biol Chem 268:3389–3395
Monaco MC, Jensen PN, Hou J, Durham LC, Major EO (1998) Detection of JC virus DNA in human tonsil tissue: evidence for site of initial viral infection. J Virol 72:9918–9923
Nevels M, Tauber B, Spruss T, Wolf H, Dobner T (2001) “Hit-and-run” transformation by adenovirus oncogenes. J Virol 75:3089–3094
Newcomb PA, Bush AC, Stoner GL, Lampe JW, Potter JD, Bigler J (2004) No evidence of an association of JC virus and colon neoplasia. Cancer Epidemiol Biomark Prev 13:662–666
Padgett BL, Walker DL (1973) Prevalence of antibodies in human sera against JC virus, an isolate from a case of progressive multifocal leukoencephalopathy. J Infect Dis 127:467–470
Price RW (1996) Neurological complications of HIV infection. Lancet 348:445–452
Rencic A, Gordon J, Otte J, Curtis M, Kovatich A, Zoltick P, Khalili K, Andrews D (1996) Detection of JC virus DNA sequence and expression of the viral oncoprotein, tumor antigen, in brain of immunocompetent patient with oligoastrocytoma. Proc Natl Acad Sci U S A 93:7352–7357
Shollar D, Del Valle L, Khalili K, Otte J, Gordon J (2004) JCV T-antigen interacts with the neurofibromatosis type 2 gene product in a transgenic mouse model of malignant peripheral nerve sheath tumors. Oncogene 23:5459–5467
Takano Y, Kato Y, van Diest PJ, Masuda M, Mitomi H, Okayasu I (2000) Cyclin D2 overexpression and lack of p27 correlate positively and cyclin E inversely with a poor prognosis in gastric cancer cases. Am J Pathol 156:585–594
Wei G, Liu CK, Atwood WJ (2000) JC virus binds to primary human glial cells, tonsillar stromal cells, and B-lymphocytes, but not to T lymphocytes. J Neurovirol 6:127–136
White MK, Khalili K (2004) Polyomaviruses and human cancer: molecular mechanisms underlying patterns of tumorigenesis. Virology 324:1–16
zur Hausen H (1999) Viruses in human cancers. Eur J Cancer 35:1878–1885
Acknowledgements
We thank Tokimasa Kumada, Hideki Hatta, Kanako Yasuyoshi, Nobuhide Hata and Hiroyo Ueda for expert technical support and Yukari Inoue for her secretarial assistance. This investigation was financially supported by a Grant-in-Aid for Basic Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hori, R., Murai, Y., Tsuneyama, K. et al. Detection of JC virus DNA sequences in colorectal cancers in Japan. Virchows Arch 447, 723–730 (2005). https://doi.org/10.1007/s00428-005-0014-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00428-005-0014-3