Skip to main content
Top
Published in: Virchows Archiv 4/2005

01-10-2005 | Original Article

Detection of JC virus DNA sequences in colorectal cancers in Japan

Authors: Ryouta Hori, Yoshihiro Murai, Kouichi Tsuneyama, Hekmat Osman Abdel-Aziz, Kazuhiro Nomoto, Hiroyuki Takahashi, Chun-mei Cheng, Tomohiko Kuchina, Brian V. Harman, Yasuo Takano

Published in: Virchows Archiv | Issue 4/2005

Login to get access

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.
Literature
1.
go back to reference 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 94:14542–14546CrossRefPubMed 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 94:14542–14546CrossRefPubMed
2.
go back to reference 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 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
3.
go back to reference 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 75:10290–10299CrossRefPubMed 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 75:10290–10299CrossRefPubMed
4.
go back to reference 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 147:676–684PubMed 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 147:676–684PubMed
5.
go back to reference 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 84:16–20PubMedCrossRef 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 84:16–20PubMedCrossRef
6.
go back to reference 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 58:895–900PubMed 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 58:895–900PubMed
7.
go back to reference 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 94:267–273PubMed 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 94:267–273PubMed
8.
go back to reference 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 9:3329–3336PubMed 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 9:3329–3336PubMed
9.
go back to reference 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 62:7093–7101PubMed 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 62:7093–7101PubMed
10.
go back to reference 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 20:4864–4870CrossRefPubMed 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 20:4864–4870CrossRefPubMed
11.
go back to reference Hara H, Kaji H (1987) Random integration of SV40 in SV40-transformed, immortalized human fibroblasts. Exp Cell Res 168:531–538PubMedCrossRef Hara H, Kaji H (1987) Random integration of SV40 in SV40-transformed, immortalized human fibroblasts. Exp Cell Res 168:531–538PubMedCrossRef
12.
go back to reference Ikegaya H, Iwase H (2004) Trial for the geographical identification using JC viral genotyping in Japan. Forensic Sci Int 139:169–172CrossRefPubMed Ikegaya H, Iwase H (2004) Trial for the geographical identification using JC viral genotyping in Japan. Forensic Sci Int 139:169–172CrossRefPubMed
13.
go back to reference Imperiale M (2001) In: Khalili K, Stoner GL (eds) The human polyoma viruses: molecular and clinical perspective. Wiley-Liss, New York, pp 53–71 Imperiale M (2001) In: Khalili K, Stoner GL (eds) The human polyoma viruses: molecular and clinical perspective. Wiley-Liss, New York, pp 53–71
14.
go back to reference 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 46:997–1004PubMedCrossRef 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 46:997–1004PubMedCrossRef
15.
go back to reference 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 72:281–289CrossRefPubMed 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 72:281–289CrossRefPubMed
16.
go back to reference Khalili K, Del Valle L, Otte J, Weaver M, Gordon J (2003) Human neurotropic polyomavirus, JCV, and its role in carcinogenesis. Oncogene 22:5181–5191PubMedCrossRef Khalili K, Del Valle L, Otte J, Weaver M, Gordon J (2003) Human neurotropic polyomavirus, JCV, and its role in carcinogenesis. Oncogene 22:5181–5191PubMedCrossRef
17.
go back to reference 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 67:223–230CrossRefPubMed 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 67:223–230CrossRefPubMed
18.
go back to reference Mandl CW, Frisque RJ (1986) Characterization of cells transformed by the human polyomavirus JC virus. J Gen Virol 67(Pt 8):1733–1739PubMedCrossRef Mandl CW, Frisque RJ (1986) Characterization of cells transformed by the human polyomavirus JC virus. J Gen Virol 67(Pt 8):1733–1739PubMedCrossRef
19.
go back to reference 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 268:3389–3395PubMed 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 268:3389–3395PubMed
20.
go back to reference 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 72:9918–9923PubMed 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 72:9918–9923PubMed
21.
go back to reference Nevels M, Tauber B, Spruss T, Wolf H, Dobner T (2001) “Hit-and-run” transformation by adenovirus oncogenes. J Virol 75:3089–3094CrossRefPubMed Nevels M, Tauber B, Spruss T, Wolf H, Dobner T (2001) “Hit-and-run” transformation by adenovirus oncogenes. J Virol 75:3089–3094CrossRefPubMed
22.
go back to reference 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 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
23.
go back to reference 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 127:467–470PubMed 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 127:467–470PubMed
25.
go back to reference 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 93:7352–7357CrossRefPubMed 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 93:7352–7357CrossRefPubMed
26.
go back to reference 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 23:5459–5467CrossRefPubMed 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 23:5459–5467CrossRefPubMed
27.
go back to reference 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 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
28.
go back to reference 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 6:127–136PubMed 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 6:127–136PubMed
29.
go back to reference White MK, Khalili K (2004) Polyomaviruses and human cancer: molecular mechanisms underlying patterns of tumorigenesis. Virology 324:1–16CrossRefPubMed White MK, Khalili K (2004) Polyomaviruses and human cancer: molecular mechanisms underlying patterns of tumorigenesis. Virology 324:1–16CrossRefPubMed
Metadata
Title
Detection of JC virus DNA sequences in colorectal cancers in Japan
Authors
Ryouta Hori
Yoshihiro Murai
Kouichi Tsuneyama
Hekmat Osman Abdel-Aziz
Kazuhiro Nomoto
Hiroyuki Takahashi
Chun-mei Cheng
Tomohiko Kuchina
Brian V. Harman
Yasuo Takano
Publication date
01-10-2005
Publisher
Springer-Verlag
Published in
Virchows Archiv / Issue 4/2005
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-005-0014-3

Other articles of this Issue 4/2005

Virchows Archiv 4/2005 Go to the issue