- Email: [email protected]
JC virus: a biomarker for colorectal cancer?
Medical Hypotheses (2002) 59(6), 667–669 ª 2002 Published by Elsevier Science Ltd. doi:10.1016/S0306-9877(02)00166-4, available online at http://www.idealibrary.com
JC virus: a biomarker for colorectal cancer? F. F. Shadan, C. Cunningham, C. R. Boland Department of Medicine and Comprehensive Cancer Center, UCSD, School of Medicine, California, USA
Summary Chromosomal instability (CIN) is present in most colorectal cancers, though the mechanism for these genetic aberrations is unclear. An explanation may lie in the possible link between JC virus (JCV) Mad-1 strain, found in colorectal cancers, and aneuploid neoplasia. It is proposed here to test the hypothesis that detection of JCV in colorectal cancer patients may serve as a clinically useful biomarker for the presence of colorectal tumors. This may be tested by looking for any correlation that may exist between JCV DNA, viral proteins, and anti-JCV anti-sera detected in samples of stool, blood, and urine obtained from patients with colorectal neoplasm compared with normal age-matched controls. ª 2002 Published by Elsevier Science Ltd. INTRODUCTION Colorectal cancer is a major cause of morbidity and mortality. The study of carcinogenesis in colorectal cancer model systems has been fundamental to our understanding of tumor biology. A paradigm has emerged in which every neoplasm is associated with some type of genomic instability to account for all of the mutations and genetic aberrations observed (1–4). Two distinct pathways have been described that lead to genomic instability. One pathway, accounting for approximately 15% of colorectal cancers has been attributed to the loss of the DNA mismatch repair (MMR) system, resulting in microsatellite instability (MSI). In the majority of colorectal cancers, the instability observed is at the chromosomal level, in the form of losses, gains, and rearrangements of whole chromosomes, thus resulting in aneuploidy and polyploidy. This form of genomic instability is referred to as chromosomal instability (CIN) (1–5).
CIN would inactivate the cell cycle checkpoint controls that normally arrest cellular growth and trigger apoptosis in response to DNA damage (3–10). Classic examples of this process are the inactivation of the p53 and retinoblastoma (Rb) tumor suppressor genes that lead to genomic instability. Mutations of p53, Rb, and related genes can be found in a major proportion of colorectal cancers. Historically, the inactivation of p53 and Rb has been demonstrated through the formation of complexes with the large transforming antigen (T-antigen) (11–14). T-antigen is the product of an oncogene encoded by the polyomavirus family of small DNA tumor viruses. Polyomaviruses have been implicated in a variety of neoplastic changes observed in humans and in animal models (15–43). JCV, which is highly homologous to both BK and to SV-40, has been associated with bladder, brain, lymphoid, and colorectal tumors. SV-40 has been associated with brain tumors and with pleural mesotheliomas. BK polyomavirus has been associated with pancreatic, renal, muscle, skeletal, lung, and brain tumors.
JC virus has the potential to cause cancer in humans The cause of chromosomal instability (CIN) remains unknown. We postulate that any mechanism(s) underlying Received 31 July 2001 Accepted 1 November 2001 Correspondence to: C.R. Boland, UCSD School of Medicine, La Jolla, CA, USA. E-mail: [email protected]
A putative link between JC virus infection and human colorectal cancer Recent evidence raises the possibility that the Mad-1 strain of JCV may play a causal role in colorectal carcinogenesis. It has been shown that the human gastrointestinal tract, and in particular the colon, serves as a major reservoir of JCV Mad-1 DNA sequences (44–46). At
667
668 Shadan et al.
least 10-fold greater viral copies have been detected in human colon cancer cells compared to matched normal controls. JCV DNA sequences have been isolated from human colon cancer xenografts grown on nude mice. The aneuploid colorectal cancer cell line, SW480, which has been regarded as a prototype for CIN, carries Mad-1 DNA sequences and expresses T-antigen (47,48). The Mad-1 strain infects normal human colon cells in culture (48). The infected cells express T-antigen and exhibit severe CIN. They appear to be dedifferentiated and immortal. These findings raise the possibility that the Mad1 strain may be involved in the etiology of colon cancer. To determine the clinical significance of these findings and to explore the possibility that JCV detection may ultimately serve as a biomarker for colorectal cancer we propose to test whether detection of Mad-1 correlates with the presence of colorectal tumors. CONCLUSION Colorectal cancer is a major cause of morbidity and mortality. The etiology of CIN, a major pathway in the development of colorectal cancer remains unknown. Preliminary evidence raises the possibility that JCV, and in particular the Mad-1 strain, may play an etiological role in this process. A link between Mad-1 and the development of colorectal cancer has yet to be established. It is proposed to test the hypothesis that Mad-1 correlates with the presence of colorectal tumors. Prospective studies can be designed to determine whether any correlation exists between JCV infection and the development of colorectal tumors. If such a link is established, then measurement of parameters such as viral DNA, proteins, or antiviral antibodies may ultimately serve as clinically useful biomarkers for the presence of colorectal tumors. REFERENCES 1. Fearon E. R., Vogelstein B. A genetic model for colorectal tumorgenesis. Cell 1990; 61: 759. 2. Lengauer C., Kinzler K. W., Vogelstein B. Genetic instability in colorectal cancers. Nature 1997; 396: 623. 3. Cahill D. P., Lengauer C., Yu J., Riggins G. J., Willson J. K., Markowitz S. D., Kinzler K. W., Vogelstein B. Mutations of mitotic checkpoint genes in human cancers. Nature 1998; 392: 300. 4. Brattain M. G., Fine W. D., Khaled F. M., Thompson J., Brattain D. E. Heterogeneity of malignant cells from a human colonic carcinoma. Cancer Res 1981; 41: 1751. 5. Branch P., Hampson R., Karran P. DNA mismatch binding defects, DNA damage tolerance, and mutator phenotype in human colorectal carcinoma cell lines. Cancer Res 1995; 55: 2304–2309. 6. Lal G., Gallinger S. Familial adenomatous polyposis. Semin Oncol 2000; 18: 314. 7. Goss K. H., Groden J. Biology of the adenomatous polyposis coli tumor suppressor. J Clin Oncol 2000; 18(9): 1967.
Medical Hypotheses (2002) 59(6), 667–669
8. Staib C., Pesch J., Gerwig R., Gerber J. K., Brehm U., Stangl A., Grummt F. P53 inhibits JC virus DNA replication in vivo and interacts with JC virus large T antigen. Virology 1996; 219(1): 237–246. 9. Dyson N., Bernards R., Friend S. H., Gooding L. R., Hassell J. A., Major E. O., Pipas J. M., Vandyke T., Harlow E. Large T-antigens of many polyomaviruses are able to form complexes with the retinoblastoma protein. J Virol 1990; 64: 1353. 10. Gannon J. V., Lane D. P. P53 and DNA polymerase alpha compete for binding to SV40 T antigen. Nature 1987; 329: 456. 11. DeCaprio J. A., Ludlow J. W., Figge J., Shew J. Y., Huang C. M., Lee W. H., Marsilio E., Paucha E., Livingston D. M. SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell 1988; 54: 275. 12. Meitz J. A., Unger T., Huibregtse J. M., Howle P. M. The transcriptional transactivation function of wild-type p53 is inhibited by SV40 large T-antigen and by HPV-16 E6 oncoprotein. EMBO J 1992; 11: 5013. 13. Agami R., Bernards R. Distinct initiation and maintenance mechanisms cooperate to induce G1 cell cycle arrest in response to DNA damage. Cell 2000; 102: 55. 14. Shadan F. F., Villarreal L. P. Co-evolution of persistently infecting small DNA viruses and their hosts is linked to hostinteractive regulatory domains. PNAS USA 1993; 90: 4117. 15. Bollag B., Chuke W. F., Frisque R. J. Hybrid genomes of the polyomavirus JC virus, BK virus, and simian virus 40: identification of sequence important for efficient transformation. J Virol 1989; 63: 863. 16. Dornreiter I., Copelaud W. C., Wang T. S. Initiation of simian virus4 0 DNA replication requires the interaction of a specific domain of human DNA polymerase alpha with large T-antigen. Mol Cell Biol 1993; 13: 809. 17. Vousden K. H. P53: Death star. Cell 2000; 103: 691. 18. Fanning E., Knippers R. Structure and function of simian virus 40 large tumor antigen. Ann Rev Biochem 1992; 61: 55. 19. Stewart N., Bacchetti S. Expression of SV40 T-antigen, but not small t antigen, is required for the induction of chromosomal aberrations in transformed human cells. Virology 1991; 180: 49. 20. Geissler E. SV-40 and human brain tumors. Prog Med Virol 1990; 37: 211–222; Genetics 1990; 63: 1. 21. Walker D. L., Frisque R. J. The Papovaviridae. In: N. P. Salzman (ed). The Polyomaviruses; vol. 1. New York: Plenum Press; 1986: . 22. Wessel R., Schweizer J., Stahl H. Simian virus 40 T-antigen DNA helicase is a hexamer which forms a binary complex during bi-directional unwinding from the viral origin of DNA replication. J Virol 1992; 66: 804. 23. Wei G., Liu C. K., Atwood W. J. JC virus binds to primary human glial cells, tonsillar stromal cells, and B-lymphocytes, but not to T lymphocytes. J Neurovirol 2000; 6(2): 127. 24. Tretiakova A., Krynska B., Gordon J., Khalili K. Human neurotropic JC virus early protein deregulates glial cell cycle pathway and impairs cell differentiation. J Neurosci Res 1999; 55(5): 588. 25. Trowbridge P. W., Frisque R. J. Analysis of G418-selected Rat2 cells containing prototype, variant, mutant, and chimeric JC virus and SV40 genomes. Virology 1993;(2): 458.
ª 2002 Published by Elsevier Science Ltd.
JC virus
26. Tumilowicz J. J., Nichols W. W., Cholon J. J., Greene A. E. Definition of a continuous human cell line derived from neuroblastoma. Cancer Res 1970; 39: 2110. 27. Valle L. D., Gordon J., Assimakopoulou M., Enam S., Geddes J. F., Varakis J. N., Katsetos C. D., Croul S., Khan Detection of JC virus DNA sequences and expression of the viral regulatory protein T-antigen in tumors of the central nervous system. Cancer Res 2001; 15(10): 4287. 28. Strizzi L., Vianale G., Guiliano M., Sacco R., Chiodera P., Casalini P., Porcopio A. SV40, JC and BK expression in tissue, urine and blood samples from patients with malignant and nonmalignant pleural disease. Anticancer Res 2000;(2A): 885. 29. Small J. A., Khoury G., Jay G., Howley P. M., Cscangos G. A. Early regions of JC virus and BK virus induce distinct and tissue-specific tumors in transgenic mice. Proc Natl Acad Sci USA 1986; 88. 30. Imperiale J. The human polyomaviruses, BKV and JCV: molecular pathogenesis of acute disease and potential role in cancer. Virology 2000; 267: 1:1. 31. Smith M. A., Strickler H. D., Granovsky M., Reaman G., Linet M., Daniel R., Shah K. V. Investigation of leukemia cells from children with common acute lymphoblastic leukemia for genomic sequences of the primate polyomaviruses JC virus, BK virus, and simian virus 40. Med Pediatr Oncol 1999; 33(5): 441. 32. Neel J. V., Major E. O., Awa A. A., Glover T., Burgess A., Traub R., Curfman B., Satoh C. Hypothesis:‘‘Rogue cell’’type chromosomal damage in lymphocytes is associated with infection with the JC human polyoma virus and has implications for oncogenesis. Proc Natl Acad Sci USA 1996; 93: 2690. 33. Neel J. V. An association in Adult Japanese between the occurrences of rogue cells among cultured lymphocytes (JC virus activity) and the frequency of ‘‘simple’’ chromosomal damage among the lymphocytes of persons exhibiting these rogue cells. Am J Hum Genet 1998; 63: 489. 34. Caldarelli-Stefano R., Boldorini R., Monga G., Meraviglia E., Zorini E. O., Ferrante P. JC virus in human glial-derived tumors. Hum Pathol 2000; 31(3): 394–395. 35. Croul S., Lublin F. D., Del Valle L., Oshinsky R. J., Giordano A., Khalili K., Ritchie C. K. The cellular response of JC virus T-antigen-induced brain tumor implants to a murine intraoccular model. J Neuroimmunol 2000; 106(1–2): 181. 36. Gordon J., Del Valle L., Otte J., Khalili K. Pituitary neoplasia induced by expression of human neurotropic polyomavirus, JCV, early genome in transgenic mice. Oncgogene 2000; 19(42): 4840. 37. Khalili D., Krynska B., Del Valle L., Katsetos C. D., Croul S. Medulloblastoma and the human neurotropic polyomavirus JC virus. Lancet 1999; 353(9159): 1152. 38. Krynska B., Del Valle L., Croul S., Giordano A., Khalili K. Detection of human neurotropic JC virus DNA sequence and
ª 2002 Published by Elsevier Science Ltd.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
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expression of the viral oncogenic protein in pediatric medulloblastomas. Proc Natl Acad Sci USA 1999; 96(20): 11519. Smith M. A., Strickler H. D., Granovsky M., Reaman G., Linet M., Daniel R., Shah K. V. Investigation of leukemia cells from children with common acute lymphoblastic leukemia for genomic sequences of the primate polyomaviruses JC virus, BK virus, and simian virus 40. Med Pediatr Oncol 1999; 33(5): 441. Weggen S., Bayer T. A., Von Deimling A., Reifenberger G., Von Schweinitz D., Wiestler O. D., Pietsch T. Low frequency of SV40, JC and BK polyomavirus sequences in human medulloblastomas, meningiomas and ependymomas. Brain Pathol 2000; 10(1): 85. Strizzi L., Vianale G., Guiliano M., Sacco R., Chiodera P., Casalini P., Procopio A. SV40, JC and BK expression in tissue, urine and blood samples from patients with malignant and nonmalignant pleural disease. Anticancer Res 2000;(2A): 885. Krynska B., Del Valle L., Croul S., Gordon J., Katsetos C. D., Carbone M., Ciordano A., Khalili K. Detection of human neurotropic JC virus DNA sequence and expression of the viral oncogene meduloblastomas. Proc Natl Acad Sci USA 2000; 96(20): 11519. Khalili K., Croul S., Del Valle L., Krynska B., Gordon J. Oncogenic potential of human neurotropic virus:laboratory and clinical observations. Isr Med Assoc J 2001; 3: 210. Laghi L., Randolph A. E., Chauhan D. P., Marra G., Major E. O., Neel J. V., Boland C. R. JC Virus is present in the mucosa of the human colon and in colorectal cancers. Proc Nat Acad Sci USA 1999; 96: 7484. Ricciardiello L., Laghi L., Ramamirtham P., Chang C. L., Chang D. K., Randolph A. E., Boland C. R. JC virus DNA sequences are frequently present in the human upper and lower gastrointestinal tract. Gastroenterology 2000; 119: 1228. Ricciardiello L., Chang D. K., Laghi L., Goel A., Chang C. L., Boland C. R. Mad-1 is the exclusive JC virus strain present in the human colon and deletes a 98-bp sequence form the transcriptional control region in colon cancers. J Virol 2001; 75(4): 1996. Shadan FF, Elbehti-Green A, Ricciardiello L, Goel A, Chang DK, Smith W, Goel A, Goodison S, Mascarello J, Boland CR. JC virus infects normal human colon cells and causes chromosomal instability (unpublished data). Ricciardiello L, Goel A, Chang DK, Shadan FF, Fionino A, Carethers JM, Laghi L, Boland CR. JC virus is integrated in SW480 colon cancer cell line and expresses T antigen: a proposed mechanism for chromosomal instability (unpublished data).
Medical Hypotheses (2002) 59(6), 667–669
JC virus: a biomarker for colorectal cancer? F. F. Shadan, C. Cunningham, C. R. Boland Department of Medicine and Comprehensive Cancer Center, UCSD, School of Medicine, California, USA
Summary Chromosomal instability (CIN) is present in most colorectal cancers, though the mechanism for these genetic aberrations is unclear. An explanation may lie in the possible link between JC virus (JCV) Mad-1 strain, found in colorectal cancers, and aneuploid neoplasia. It is proposed here to test the hypothesis that detection of JCV in colorectal cancer patients may serve as a clinically useful biomarker for the presence of colorectal tumors. This may be tested by looking for any correlation that may exist between JCV DNA, viral proteins, and anti-JCV anti-sera detected in samples of stool, blood, and urine obtained from patients with colorectal neoplasm compared with normal age-matched controls. ª 2002 Published by Elsevier Science Ltd. INTRODUCTION Colorectal cancer is a major cause of morbidity and mortality. The study of carcinogenesis in colorectal cancer model systems has been fundamental to our understanding of tumor biology. A paradigm has emerged in which every neoplasm is associated with some type of genomic instability to account for all of the mutations and genetic aberrations observed (1–4). Two distinct pathways have been described that lead to genomic instability. One pathway, accounting for approximately 15% of colorectal cancers has been attributed to the loss of the DNA mismatch repair (MMR) system, resulting in microsatellite instability (MSI). In the majority of colorectal cancers, the instability observed is at the chromosomal level, in the form of losses, gains, and rearrangements of whole chromosomes, thus resulting in aneuploidy and polyploidy. This form of genomic instability is referred to as chromosomal instability (CIN) (1–5).
CIN would inactivate the cell cycle checkpoint controls that normally arrest cellular growth and trigger apoptosis in response to DNA damage (3–10). Classic examples of this process are the inactivation of the p53 and retinoblastoma (Rb) tumor suppressor genes that lead to genomic instability. Mutations of p53, Rb, and related genes can be found in a major proportion of colorectal cancers. Historically, the inactivation of p53 and Rb has been demonstrated through the formation of complexes with the large transforming antigen (T-antigen) (11–14). T-antigen is the product of an oncogene encoded by the polyomavirus family of small DNA tumor viruses. Polyomaviruses have been implicated in a variety of neoplastic changes observed in humans and in animal models (15–43). JCV, which is highly homologous to both BK and to SV-40, has been associated with bladder, brain, lymphoid, and colorectal tumors. SV-40 has been associated with brain tumors and with pleural mesotheliomas. BK polyomavirus has been associated with pancreatic, renal, muscle, skeletal, lung, and brain tumors.
JC virus has the potential to cause cancer in humans The cause of chromosomal instability (CIN) remains unknown. We postulate that any mechanism(s) underlying Received 31 July 2001 Accepted 1 November 2001 Correspondence to: C.R. Boland, UCSD School of Medicine, La Jolla, CA, USA. E-mail: [email protected]
A putative link between JC virus infection and human colorectal cancer Recent evidence raises the possibility that the Mad-1 strain of JCV may play a causal role in colorectal carcinogenesis. It has been shown that the human gastrointestinal tract, and in particular the colon, serves as a major reservoir of JCV Mad-1 DNA sequences (44–46). At
667
668 Shadan et al.
least 10-fold greater viral copies have been detected in human colon cancer cells compared to matched normal controls. JCV DNA sequences have been isolated from human colon cancer xenografts grown on nude mice. The aneuploid colorectal cancer cell line, SW480, which has been regarded as a prototype for CIN, carries Mad-1 DNA sequences and expresses T-antigen (47,48). The Mad-1 strain infects normal human colon cells in culture (48). The infected cells express T-antigen and exhibit severe CIN. They appear to be dedifferentiated and immortal. These findings raise the possibility that the Mad1 strain may be involved in the etiology of colon cancer. To determine the clinical significance of these findings and to explore the possibility that JCV detection may ultimately serve as a biomarker for colorectal cancer we propose to test whether detection of Mad-1 correlates with the presence of colorectal tumors. CONCLUSION Colorectal cancer is a major cause of morbidity and mortality. The etiology of CIN, a major pathway in the development of colorectal cancer remains unknown. Preliminary evidence raises the possibility that JCV, and in particular the Mad-1 strain, may play an etiological role in this process. A link between Mad-1 and the development of colorectal cancer has yet to be established. It is proposed to test the hypothesis that Mad-1 correlates with the presence of colorectal tumors. Prospective studies can be designed to determine whether any correlation exists between JCV infection and the development of colorectal tumors. If such a link is established, then measurement of parameters such as viral DNA, proteins, or antiviral antibodies may ultimately serve as clinically useful biomarkers for the presence of colorectal tumors. REFERENCES 1. Fearon E. R., Vogelstein B. A genetic model for colorectal tumorgenesis. Cell 1990; 61: 759. 2. Lengauer C., Kinzler K. W., Vogelstein B. Genetic instability in colorectal cancers. Nature 1997; 396: 623. 3. Cahill D. P., Lengauer C., Yu J., Riggins G. J., Willson J. K., Markowitz S. D., Kinzler K. W., Vogelstein B. Mutations of mitotic checkpoint genes in human cancers. Nature 1998; 392: 300. 4. Brattain M. G., Fine W. D., Khaled F. M., Thompson J., Brattain D. E. Heterogeneity of malignant cells from a human colonic carcinoma. Cancer Res 1981; 41: 1751. 5. Branch P., Hampson R., Karran P. DNA mismatch binding defects, DNA damage tolerance, and mutator phenotype in human colorectal carcinoma cell lines. Cancer Res 1995; 55: 2304–2309. 6. Lal G., Gallinger S. Familial adenomatous polyposis. Semin Oncol 2000; 18: 314. 7. Goss K. H., Groden J. Biology of the adenomatous polyposis coli tumor suppressor. J Clin Oncol 2000; 18(9): 1967.
Medical Hypotheses (2002) 59(6), 667–669
8. Staib C., Pesch J., Gerwig R., Gerber J. K., Brehm U., Stangl A., Grummt F. P53 inhibits JC virus DNA replication in vivo and interacts with JC virus large T antigen. Virology 1996; 219(1): 237–246. 9. Dyson N., Bernards R., Friend S. H., Gooding L. R., Hassell J. A., Major E. O., Pipas J. M., Vandyke T., Harlow E. Large T-antigens of many polyomaviruses are able to form complexes with the retinoblastoma protein. J Virol 1990; 64: 1353. 10. Gannon J. V., Lane D. P. P53 and DNA polymerase alpha compete for binding to SV40 T antigen. Nature 1987; 329: 456. 11. DeCaprio J. A., Ludlow J. W., Figge J., Shew J. Y., Huang C. M., Lee W. H., Marsilio E., Paucha E., Livingston D. M. SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell 1988; 54: 275. 12. Meitz J. A., Unger T., Huibregtse J. M., Howle P. M. The transcriptional transactivation function of wild-type p53 is inhibited by SV40 large T-antigen and by HPV-16 E6 oncoprotein. EMBO J 1992; 11: 5013. 13. Agami R., Bernards R. Distinct initiation and maintenance mechanisms cooperate to induce G1 cell cycle arrest in response to DNA damage. Cell 2000; 102: 55. 14. Shadan F. F., Villarreal L. P. Co-evolution of persistently infecting small DNA viruses and their hosts is linked to hostinteractive regulatory domains. PNAS USA 1993; 90: 4117. 15. Bollag B., Chuke W. F., Frisque R. J. Hybrid genomes of the polyomavirus JC virus, BK virus, and simian virus 40: identification of sequence important for efficient transformation. J Virol 1989; 63: 863. 16. Dornreiter I., Copelaud W. C., Wang T. S. Initiation of simian virus4 0 DNA replication requires the interaction of a specific domain of human DNA polymerase alpha with large T-antigen. Mol Cell Biol 1993; 13: 809. 17. Vousden K. H. P53: Death star. Cell 2000; 103: 691. 18. Fanning E., Knippers R. Structure and function of simian virus 40 large tumor antigen. Ann Rev Biochem 1992; 61: 55. 19. Stewart N., Bacchetti S. Expression of SV40 T-antigen, but not small t antigen, is required for the induction of chromosomal aberrations in transformed human cells. Virology 1991; 180: 49. 20. Geissler E. SV-40 and human brain tumors. Prog Med Virol 1990; 37: 211–222; Genetics 1990; 63: 1. 21. Walker D. L., Frisque R. J. The Papovaviridae. In: N. P. Salzman (ed). The Polyomaviruses; vol. 1. New York: Plenum Press; 1986: . 22. Wessel R., Schweizer J., Stahl H. Simian virus 40 T-antigen DNA helicase is a hexamer which forms a binary complex during bi-directional unwinding from the viral origin of DNA replication. J Virol 1992; 66: 804. 23. Wei G., Liu C. K., Atwood W. J. JC virus binds to primary human glial cells, tonsillar stromal cells, and B-lymphocytes, but not to T lymphocytes. J Neurovirol 2000; 6(2): 127. 24. Tretiakova A., Krynska B., Gordon J., Khalili K. Human neurotropic JC virus early protein deregulates glial cell cycle pathway and impairs cell differentiation. J Neurosci Res 1999; 55(5): 588. 25. Trowbridge P. W., Frisque R. J. Analysis of G418-selected Rat2 cells containing prototype, variant, mutant, and chimeric JC virus and SV40 genomes. Virology 1993;(2): 458.
ª 2002 Published by Elsevier Science Ltd.
JC virus
26. Tumilowicz J. J., Nichols W. W., Cholon J. J., Greene A. E. Definition of a continuous human cell line derived from neuroblastoma. Cancer Res 1970; 39: 2110. 27. Valle L. D., Gordon J., Assimakopoulou M., Enam S., Geddes J. F., Varakis J. N., Katsetos C. D., Croul S., Khan Detection of JC virus DNA sequences and expression of the viral regulatory protein T-antigen in tumors of the central nervous system. Cancer Res 2001; 15(10): 4287. 28. Strizzi L., Vianale G., Guiliano M., Sacco R., Chiodera P., Casalini P., Porcopio A. SV40, JC and BK expression in tissue, urine and blood samples from patients with malignant and nonmalignant pleural disease. Anticancer Res 2000;(2A): 885. 29. Small J. A., Khoury G., Jay G., Howley P. M., Cscangos G. A. Early regions of JC virus and BK virus induce distinct and tissue-specific tumors in transgenic mice. Proc Natl Acad Sci USA 1986; 88. 30. Imperiale J. The human polyomaviruses, BKV and JCV: molecular pathogenesis of acute disease and potential role in cancer. Virology 2000; 267: 1:1. 31. Smith M. A., Strickler H. D., Granovsky M., Reaman G., Linet M., Daniel R., Shah K. V. Investigation of leukemia cells from children with common acute lymphoblastic leukemia for genomic sequences of the primate polyomaviruses JC virus, BK virus, and simian virus 40. Med Pediatr Oncol 1999; 33(5): 441. 32. Neel J. V., Major E. O., Awa A. A., Glover T., Burgess A., Traub R., Curfman B., Satoh C. Hypothesis:‘‘Rogue cell’’type chromosomal damage in lymphocytes is associated with infection with the JC human polyoma virus and has implications for oncogenesis. Proc Natl Acad Sci USA 1996; 93: 2690. 33. Neel J. V. An association in Adult Japanese between the occurrences of rogue cells among cultured lymphocytes (JC virus activity) and the frequency of ‘‘simple’’ chromosomal damage among the lymphocytes of persons exhibiting these rogue cells. Am J Hum Genet 1998; 63: 489. 34. Caldarelli-Stefano R., Boldorini R., Monga G., Meraviglia E., Zorini E. O., Ferrante P. JC virus in human glial-derived tumors. Hum Pathol 2000; 31(3): 394–395. 35. Croul S., Lublin F. D., Del Valle L., Oshinsky R. J., Giordano A., Khalili K., Ritchie C. K. The cellular response of JC virus T-antigen-induced brain tumor implants to a murine intraoccular model. J Neuroimmunol 2000; 106(1–2): 181. 36. Gordon J., Del Valle L., Otte J., Khalili K. Pituitary neoplasia induced by expression of human neurotropic polyomavirus, JCV, early genome in transgenic mice. Oncgogene 2000; 19(42): 4840. 37. Khalili D., Krynska B., Del Valle L., Katsetos C. D., Croul S. Medulloblastoma and the human neurotropic polyomavirus JC virus. Lancet 1999; 353(9159): 1152. 38. Krynska B., Del Valle L., Croul S., Giordano A., Khalili K. Detection of human neurotropic JC virus DNA sequence and
ª 2002 Published by Elsevier Science Ltd.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
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expression of the viral oncogenic protein in pediatric medulloblastomas. Proc Natl Acad Sci USA 1999; 96(20): 11519. Smith M. A., Strickler H. D., Granovsky M., Reaman G., Linet M., Daniel R., Shah K. V. Investigation of leukemia cells from children with common acute lymphoblastic leukemia for genomic sequences of the primate polyomaviruses JC virus, BK virus, and simian virus 40. Med Pediatr Oncol 1999; 33(5): 441. Weggen S., Bayer T. A., Von Deimling A., Reifenberger G., Von Schweinitz D., Wiestler O. D., Pietsch T. Low frequency of SV40, JC and BK polyomavirus sequences in human medulloblastomas, meningiomas and ependymomas. Brain Pathol 2000; 10(1): 85. Strizzi L., Vianale G., Guiliano M., Sacco R., Chiodera P., Casalini P., Procopio A. SV40, JC and BK expression in tissue, urine and blood samples from patients with malignant and nonmalignant pleural disease. Anticancer Res 2000;(2A): 885. Krynska B., Del Valle L., Croul S., Gordon J., Katsetos C. D., Carbone M., Ciordano A., Khalili K. Detection of human neurotropic JC virus DNA sequence and expression of the viral oncogene meduloblastomas. Proc Natl Acad Sci USA 2000; 96(20): 11519. Khalili K., Croul S., Del Valle L., Krynska B., Gordon J. Oncogenic potential of human neurotropic virus:laboratory and clinical observations. Isr Med Assoc J 2001; 3: 210. Laghi L., Randolph A. E., Chauhan D. P., Marra G., Major E. O., Neel J. V., Boland C. R. JC Virus is present in the mucosa of the human colon and in colorectal cancers. Proc Nat Acad Sci USA 1999; 96: 7484. Ricciardiello L., Laghi L., Ramamirtham P., Chang C. L., Chang D. K., Randolph A. E., Boland C. R. JC virus DNA sequences are frequently present in the human upper and lower gastrointestinal tract. Gastroenterology 2000; 119: 1228. Ricciardiello L., Chang D. K., Laghi L., Goel A., Chang C. L., Boland C. R. Mad-1 is the exclusive JC virus strain present in the human colon and deletes a 98-bp sequence form the transcriptional control region in colon cancers. J Virol 2001; 75(4): 1996. Shadan FF, Elbehti-Green A, Ricciardiello L, Goel A, Chang DK, Smith W, Goel A, Goodison S, Mascarello J, Boland CR. JC virus infects normal human colon cells and causes chromosomal instability (unpublished data). Ricciardiello L, Goel A, Chang DK, Shadan FF, Fionino A, Carethers JM, Laghi L, Boland CR. JC virus is integrated in SW480 colon cancer cell line and expresses T antigen: a proposed mechanism for chromosomal instability (unpublished data).
Medical Hypotheses (2002) 59(6), 667–669