Viral carcinogenesis and genomic instability

  • Karl Münger
  • Hiroyuki Hayakawa
  • Christine L. Nguyen
  • Nadja V. Melquiot
  • Anette Duensing
  • Stefan Duensing
Part of the Experientia Supplementum book series (EXS, volume 96)


Oncogenes encoded by human tumor viruses play integral roles in the viral conquest of the host cell by subverting crucial and relatively non-redundant regulatory circuits that regulate cellular proliferation, differentiation, apoptosis and life span. Human tumor virus oncoproteins can also disrupt pathways that are necessary for the maintenance of the integrity of host cellular genome. Some viral oncoproteins act as powerful mutator genes and their expression dramatically increases the incidence of host cell mutations with every round of cell division. Others subvert cellular safeguard mechanisms intended to eliminate cells that have acquired abnormalities that interfere with normal cell division. Viruses that encode such activities can contribute to initiation as well as progression of human cancers.


Aneuploidy centrosomes cervical cancer human papillomavirus tumor suppressor viral oncogene 


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  1. 1.
    Weinberg RA (1997) The cat and mouse games that genes, viruses, and cells play. Cell 88: 573–575CrossRefPubMedGoogle Scholar
  2. 2.
    zur Hausen H (2001) Proliferation-inducing viruses in non-permissive systems as possible causes of human cancers. Lancet 357: 381–384PubMedGoogle Scholar
  3. 3.
    zur Hausen H (2001) Oncogenic DNA viruses. Oncogene 20: 7820–7823PubMedGoogle Scholar
  4. 4.
    Nevins JR (2001) Cell Transformation by Viruses. In: DM Knipe, PM Howley (eds): Fields Virology. Lippincott-Williams and Wikins, Philadelphia, 245–283Google Scholar
  5. 5.
    Parada LF, Tabin CJ, Shih C, Weinberg RA (1982) Human EJ bladder carcinoma oncogene is homologue of Harvey sarcoma virus ras gene. Nature 297: 474–478CrossRefPubMedGoogle Scholar
  6. 6.
    Howley PM, Lowy DR (2001) Papillomaviruses and their replication. In: DM Knipe, PM Howley (eds): Fields Virology. Lippincott Williams and Wilkins, Philadelphia, 2197–2229Google Scholar
  7. 7.
    de Villiers EM, Fauquet C, Broker TR, Bernard HU, zur Hausen H (2004) Classification of papillomaviruses. Virology 324: 17–27PubMedGoogle Scholar
  8. 8.
    zur Hyausen H (2002) Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2: 342–350Google Scholar
  9. 9.
    Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, Zahurak ML, Daniel RW, Viglione M, Symer DE et al. (2000) Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 92: 709–720CrossRefPubMedGoogle Scholar
  10. 10.
    Crum CP, McLachlin CM, Tate JE, Mutter GL (1997) Pathobiology of vulvar squamous neoplasia. Curr Opin Obstet Gynecol 9: 63–69PubMedGoogle Scholar
  11. 11.
    Klencke BJ, Palefsky JM (2003) Anal cancer: an HIV-associated cancer. Hematol Oncol Clin North Am 17: 859–872CrossRefPubMedGoogle Scholar
  12. 12.
    Koutsky LA, Ault KA, Wheeler CM, Brown DR, Barr E, Alvarez FB, Chiacchierini LM, Jansen KU (2002) A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med 347: 1645–1651CrossRefPubMedGoogle Scholar
  13. 13.
    Frazer IH (2004) Prevention of cervical cancer through papillomavirus vaccination. Nat Rev Immunol 4: 46–54CrossRefPubMedGoogle Scholar
  14. 14.
    Dyson N, Howley PM, Münger K, Harlow E (1989) The human papillomavirus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science 243: 934–937PubMedGoogle Scholar
  15. 15.
    Werness BA, Levine AJ, Howley PM (1990) Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science 248: 76–79PubMedGoogle Scholar
  16. 16.
    Klingelhutz AJ, Foster SA, McDougall JK (1996) Telomerase activation by the E6 gene product of human papillomavirus type 16. Nature 380: 79–82CrossRefPubMedGoogle Scholar
  17. 17.
    Winer RL, Lee SK, Hughes JP, Adam DE, Kiviat NB, Koutsky LA (2003) Genital human papillomavirus infection: incidence and risk factors in a cohort of female university students. Am J Epidemiol 157: 218–226CrossRefPubMedGoogle Scholar
  18. 18.
    Lowy DR, Howley PM (2001) Papillomaviruses. In: DM Knipe, PM Howley (eds): Fields Virology Lippincott Williams and Wilkins, Philadelphia, 2231–2264Google Scholar
  19. 19.
    Thorland EC, Myers SL, Gostout BS, Smith DI (2003) Common fragile sites are preferential targets for HPV16 integrations in cervical tumors. Oncogene 22: 1225–1237CrossRefPubMedGoogle Scholar
  20. 20.
    Wentzensen N, Vinokurova S, von Knebel Doeberitz M (2004) Systematic review of genomic integration sites of human papillomavirus genomes in epithelial dysplasia and invasive cancer of the female lower genital tract. Cancer Res 64: 3878–3884CrossRefPubMedGoogle Scholar
  21. 21.
    Jeon S, Allen-Hoffmann BL, Lambert PF (1995) Integration of human papillomavirus type 16 into the human genome correlates with a selective growth advantage of cells. J Virol 69: 2989–2997PubMedGoogle Scholar
  22. 22.
    Munger K, Baldwin A, Edwards KM, Hayakawa H, Nguyen CL, Owens M, Grace M, Huh KW (2004) Mechanisms of human papillomavirus-induced oncogensis. J Virol 78: 11451–11460CrossRefPubMedGoogle Scholar
  23. 23.
    Hawley-Nelson P, Vousden KH, Hubbert NL, Lowy DR, Schiller JT (1989) HPV16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes. EMBO J 8: 3905–3910PubMedGoogle Scholar
  24. 24.
    Münger K, Phelps WC, Bubb V, Howley PM, Schlegel R (1989) The E6 and E7 genes of the human papillomavirus type 16_together are necessary and sufficient for transformation of primary human keratinocytes. J Virol 63: 4417–4421PubMedGoogle Scholar
  25. 25.
    McCance DJ, Kopan R, Fuchs E, Laimins LA (1988) Human papillomavirus type 16 alters human epithelial cell differentiation in vitro. Proc Natl Acad Sci USA 85: 7169–7173PubMedGoogle Scholar
  26. 26.
    Arbeit JM, Howley PM, Hanahan D (1996) Chronic estrogen-induced cervical and vaginal squamous carcinogenesis in human papillomavirus type 16 transgenic mice. Proc Natl Acad Sci USA 93: 2930–2935CrossRefPubMedGoogle Scholar
  27. 27.
    Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100: 57–70CrossRefPubMedGoogle Scholar
  28. 28.
    Klausner RD (2002) The fabric of cancer cell biology-Weaving together the strands. Cancer Cell 1: 3–10CrossRefPubMedGoogle Scholar
  29. 29.
    Cahill DP, Kinzler KW, Vogelstein B, Lengauer C (1999) Genetic instability and darwinian selection in tumours. Trends Cell Biol 9: M57–M60CrossRefPubMedGoogle Scholar
  30. 30.
    Hahn WC, Weinberg RA (2002) Rules for making human tumor cells. N Engl J Med 347: 1593–1603CrossRefPubMedGoogle Scholar
  31. 31.
    Zimonjic D, Brooks MW, Popescu N, Weinberg RA, Hahn WC (2001) Derivation of human tumor cells in vitro without widespread genomic instability. Cancer Res 61: 8838–8844PubMedGoogle Scholar
  32. 32.
    Nowak MA, Komarova NL, Sengupta A, Jallepalli PV, Shih Ie M, Vogelstein B, Lengauer C (2002) The role of chromosomal instability in tumor initiation. Proc Natl Acad Sci USA 99: 16226–16231CrossRefPubMedGoogle Scholar
  33. 33.
    Kinzler KW, Vogelstein B (1997) Cancer-susceptibility genes. Gatekeepers and caretakers. Nature 386: 761, 763CrossRefPubMedGoogle Scholar
  34. 34.
    Loeb LA (1991) Mutator phenotype may be required for multistage carcinogenesis. Cancer Res 51: 3075–3079PubMedGoogle Scholar
  35. 35.
    Tomlinson IP, Novelli MR, Bodmer WF (1996) The mutation rate and cancer. Proc Natl Acad Sci USA 93: 14800–14803CrossRefPubMedGoogle Scholar
  36. 36.
    Duensing S, Munger K (2003) Centrosomes, genomic instability, and cervical carcinogenesis. Crit Rev Eukaryot Gene Expr 13: 9–23CrossRefPubMedGoogle Scholar
  37. 37.
    White AE, Livanos EM, Tlsty TD (1994) Differential Disruption of Genomic Integrity and Cell Cycle Regulation in Normal Human Fibroblasts by the HPV Oncoproteins. Genes and Develop 8: 666–677Google Scholar
  38. 38.
    Duensing S, Munger K (2004) Mechanisms of genomic instability in human cancer: insights from studies with human papillomavirus oncoproteins. Int J Cancer 109: 157–162CrossRefPubMedGoogle Scholar
  39. 39.
    Southern SA, Evans MF, Herrington CS (1997) Basal cell tetrasomy in low-grade cervical squamous intraepithelial lesions infected with high-risk human papillomaviruses. Cancer Res 57: 4210–4213PubMedGoogle Scholar
  40. 40.
    Giannoudis A, Evans MF, Southern SA, Herrington CS (2000) Basal keratinocyte tetrasomy in low-grade squamous intra-epithelial lesions of the cervix is restricted to high and intermediate risk HPV infection but is not type-specific. Br J Cancer 82: 424–428CrossRefPubMedGoogle Scholar
  41. 41.
    Southern SA, Noya F, Meyers C, Broker TR, Chow LT, Herrington CS (2001) Tetrasomy is induced by human papillomavirus type 18 E7 gene expression in keratinocyte raft cultures. Cancer Res 61: 4858–4863PubMedGoogle Scholar
  42. 42.
    Southern SA, Lewis MH, Herrington CS (2004) Induction of tetrasomy by human papillomavirus type 16 E7 protein is independent of pRb binding and disruption of differentiation. Br J Cancer 90: 1949–1954CrossRefPubMedGoogle Scholar
  43. 43.
    Meraldi P, Honda R, Nigg EA (2002) Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53(-/-) cells. Embo J 21: 483–492CrossRefPubMedGoogle Scholar
  44. 44.
    Storchova Z, Pellman D (2004) From polyploidy to aneuploidy, genome instability and cancer. Nat Rev Mol Cell Biol 5: 45–54CrossRefPubMedGoogle Scholar
  45. 45.
    Winkler B, Crum CP, Fujii T, Ferenczy A, Boon M, Braun L, Lancaster WD, Richart RM (1984) Koilocytotic lesions of the cervix. The relationship of mitotic abnormalities to the presence of papillomavirus antigens and nuclear DNA content. Cancer 53: 1081–1087PubMedGoogle Scholar
  46. 46.
    Hinchcliffe EH, Sluder G (2001) “It Takes Two to Tango”: understanding how centrosome duplication is regulated throughout the cell cycle. Genes Dev 15: 1167–1181CrossRefPubMedGoogle Scholar
  47. 47.
    Nigg EA (2002) Centrosome aberrations: cause or consequence of cancer progression? Nat Rev Cancer 2: 815–825CrossRefPubMedGoogle Scholar
  48. 48.
    Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown JP, Sedivy JM, Kinzler KW, Vogelstein B (1998) Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science 282: 1497–1501CrossRefPubMedGoogle Scholar
  49. 49.
    Duensing S, Lee LY, Duensing A, Basile J, Piboonniyom S, Gonzalez S, Crum CP, Munger K (2000) The human papillomavirus type 16 E6 and E7 oncoproteins cooperate to induce mitotic defects and genomic instability by uncoupling centrosome duplication from the cell division cycle. Proc Natl Acad Sci USA 97: 10002–10007CrossRefPubMedGoogle Scholar
  50. 50.
    Boveri T (1900) Zellenstudien IV. Über die Natur der Zentrosomen. G. Fischer, JenaGoogle Scholar
  51. 51.
    Boveri T (1902) Über mehrpolige Mitosen als Mittel zur Analyse des Zellkerns. Verh d phys-med Ges Würzburg NF 35: 67–90Google Scholar
  52. 52.
    Hansemann D (1890) Ueber asymmetrische Zelltheilung in Epithelkrebsen und deren biologische Bedeutung. Arch Pathol Anat Physiol Klin Med 119: 299–326Google Scholar
  53. 53.
    Boveri T (1914) Zur Frage der Entstehung Maligner Tumoren. Fischer, JenaGoogle Scholar
  54. 54.
    Skyldberg B, Fujioka K, Hellstrom AC, Sylven L, Moberger B, Auer G (2001) Human papillomavirus infection, centrosome aberration, and genetic stability in cervical lesions. Mod Pathol 14: 279–284CrossRefPubMedGoogle Scholar
  55. 55.
    Duensing S, Duensing A, Flores ER, Do A, Lambert PF, Munger K (2001) Centrosome abnormalities and genomic instability by episomal expression of human papillomavirus type 16 in raft cultures of human keratinocytes. J Virol 75: 7712–7716CrossRefPubMedGoogle Scholar
  56. 56.
    Duensing S, Duensing A, Crum CP, Munger K (2001) Human papillomavirus type 16 E7 oncoprotein-induced abnormal centrosome synthesis is an early event in the evolving malignant phenotype. Cancer Res 61: 2356–2360PubMedGoogle Scholar
  57. 57.
    Brinkley BR (2001) Managing the centrosome numbers game: from chaos to stability in cancer cell division. Trends Cell Biol 11: 18–21CrossRefPubMedGoogle Scholar
  58. 58.
    Schaeffer AJ, Nguyen M, Liem A, Lee D, Montagna C, Lambert PF, Ried T, Difilippantonio MJ (2004) E6 and E7 oncoproteins induce distinct patterns of chromosomal aneuploidy in skin tumors from transgenic mice. Cancer Res 64: 538–546CrossRefPubMedGoogle Scholar
  59. 59.
    Riley RR, Duensing S, Brake T, Munger K, Lambert PF, Arbeit JM (2003) Dissection of human papillomavirus E6 and E7 function in transgenic mouse models of cervical carcinogenesis. Cancer Res 63: 4862–4871PubMedGoogle Scholar
  60. 60.
    Hernando E, Nahle Z, Juan G, Diaz-Rodriguez E, Alaminos M, Hemann M, Michel L, Mittal V, Gerald W, Benezra R et al. (2004) Rb inactivation promotes genomic instability by uncoupling cell cycle progression from mitotic control. Nature 430: 797–802CrossRefPubMedGoogle Scholar
  61. 61.
    Duensing S, Munger K (2003) Human papillomavirus type 16 E7 oncoprotein can induce abnormal centrosome duplication through a mechanism independent of retinoblastoma protein family members. J Virol 77: 12331–12335CrossRefPubMedGoogle Scholar
  62. 62.
    Duensing S, Duensing A, Lee DC, Edwards KM, Piboonniyom S, Manuel E, Skaltsounis L, Meijer L, Munger K (2004) The cyclin-dependent kinase inhibitor indirubin-3’-oxime selectively inhibits human papillomavirus type 16 E7-induced numerical centrosome anomalies. Oncogene 23: 8206–8215PubMedGoogle Scholar
  63. 63.
    Ortega S, Prieto I, Odajima J, Martin A, Dubus P, Sotillo R, Barbero JL, Malumbres M, Barbacid M (2003) Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice. Nat Genet 35: 25–31CrossRefPubMedGoogle Scholar
  64. 64.
    Tetsu O, McCormick F (2003) Proliferation of cancer cells despite CDK2_inhibition. Cancer Cell 3: 233–245CrossRefPubMedGoogle Scholar
  65. 65.
    Duensing S, Münger K (2002) The human papillomavirus type 16 E6 and E7 oncoproteins independently induce numerical and structural chromosome instability. Cancer Res 62: 7075–7082PubMedGoogle Scholar
  66. 66.
    McClintock B (1940) The stability of broken ends of chromosomes in Zea mays. Genetics 26: 234–282Google Scholar
  67. 67.
    Hackett JA, Feldser DM, Greider CW (2001) Telomere dysfunction increases mutation rate and genomic instability. Cell 106: 275–286CrossRefPubMedGoogle Scholar
  68. 68.
    Kessis TD, Connolly DC, Hedrick L, Cho KR (1996) Expression of HPV16 E6 or E7 increases integration of foreign DNA. Oncogene 13: 427–431PubMedGoogle Scholar
  69. 69.
    Iftner T, Elbel M, Schopp B, Hiller T, Loizou JI, Caldecott KW, Stubenrauch F (2002) Interference of papillomavirus E6 protein with single-strand break repair by interaction with XRCC1. Embo J 21: 4741–4748CrossRefPubMedGoogle Scholar
  70. 70.
    Thompson DA, Belinsky G, Chang TH-T, Jones DL, Schlegel R, Münger K (1997) The human papillomavirus-16 E6 oncoprotein decreases the vigilance of mitotic checkpoints. Oncogene 15: 3025–3036CrossRefPubMedGoogle Scholar
  71. 71.
    Thomas JT, Laimins LA (1998) Human papillomavirus oncoproteins E6 and E7 independently abrogate the mitotic spindle checkpoint. J Virol 72: 1131–1137PubMedGoogle Scholar
  72. 72.
    Patel D, Incassati A, Wang N, McCance DJ (2004) Human papillomavirus type 16 E6 and E7 cause polyploidy in human keratinocytes and up-regulation of G2-M-phase proteins. Cancer Res 64: 1299–1306CrossRefPubMedGoogle Scholar
  73. 73.
    Thierry F, Benotmane MA, Demeret C, Mori M, Teissier S, Desaintes C (2004) A genomic approach reveals a novel mitotic pathway in papillomavirus carcinogenesis. Cancer Res 64: 895–903CrossRefPubMedGoogle Scholar
  74. 74.
    Tsukasaki K (2002) Genetic instability of adult T-cell leukemia/lymphoma by comparative genomic hybridization analysis. J Clin Immunol 22: 57–63CrossRefPubMedGoogle Scholar
  75. 75.
    Tsukasaki K, Krebs J, Nagai K, Tomonaga M, Koeffler HP, Bartram CR, Jauch A (2001) Comparative genomic hybridization analysis in adult T-cell leukemia/lymphoma: correlation with clinical course. Blood 97: 3875–3881CrossRefPubMedGoogle Scholar
  76. 76.
    Jin DY, Spencer F, Jeang KT (1998) Human T cell leukemia virus type 1 oncoprotein Tax targets the human mitotic checkpoint protein MAD1. Cell 93: 81–91CrossRefPubMedGoogle Scholar
  77. 77.
    Haoudi A, Daniels RC, Wong E, Kupfer G, Semmes OJ (2003) Human T-cell leukemia virus-I tax oncoprotein functionally targets a subnuclear complex involved in cellular DNA damageresponse. J Biol Chem 278: 37736–37744CrossRefPubMedGoogle Scholar
  78. 78.
    Semmes OJ, Jeang KT (1996) Localization of human T-cell leukemia virus type 1 tax to subnuclear compartments that overlap with interchromatin speckles. J Virol 70: 6347–6357PubMedGoogle Scholar
  79. 79.
    Park HU, Jeong JH, Chung JH, Brady JN (2004) Human T-cell leukemia virus type 1 Tax interacts with Chk1 and attenuates DNA-damage induced G2 arrest mediated by Chk1. Oncogene 23: 4966–4974PubMedGoogle Scholar
  80. 80.
    Jeang KT, Giam CZ, Majone F, Aboud M (2004) Life, death, and tax: role of HTLV-I oncoprotein in genetic instability and cellular transformation. J Biol Chem 279: 31991–31994CrossRefPubMedGoogle Scholar
  81. 81.
    Lemoine FJ, Marriott SJ (2002) Genomic instability driven by the human T-cell leukemia virus type I (HTLV-I) oncoprotein, Tax. Oncogene 21: 7230–7234CrossRefPubMedGoogle Scholar
  82. 82.
    Shimura M, Onozuka Y, Yamaguchi T, Hatake K, Takaku F, Ishizaka Y (1999) Micronuclei formation with chromosome breaks and gene amplification caused by Vpr, an accessory gene of human immunodeficiency virus. Cancer Res 59: 2259–2264PubMedGoogle Scholar
  83. 83.
    Shimura M, Tanaka Y, Nakamura S, Minemoto Y, Yamashita K, Hatake K, Takaku F, Ishizaka Y (1999) Micronuclei formation and aneuploidy induced by Vpr, an accessory gene of human immunodeficiency virus type 1. Faseb J 13: 621–637PubMedGoogle Scholar
  84. 84.
    Minemoto Y, Shimura M, Ishizaka Y, Masamune Y, Yamashita K (1999) Multiple centrosome formation induced by the expression of Vpr gene of human immunodeficiency virus. Biochem Biophys Res Commun 258: 379–384CrossRefPubMedGoogle Scholar
  85. 85.
    Rickinson AB, Kieff E (2001) Epstein-Barr Virus. In: DM Knipe, PM Howley (eds): Fields Virology. Lippincott Williams and Wilkins, Philadelphia, 2575–2627Google Scholar
  86. 86.
    Liu MT, Chen YR, Chen SC, Hu CY, Lin CS, Chang YT, Wang WB, Chen JY (2004) Epstein-Barr virus latent membrane protein 1 induces micronucleus formation, represses DNA repair and enhances sensitivity to DNA-damaging agents in human epithelial cells. Oncogene 23: 2531–2539PubMedGoogle Scholar
  87. 87.
    Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, Moore PS (1994) Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science 266: 1865–1869PubMedGoogle Scholar
  88. 88.
    Moore PS, Chang YE (2001) Kaposi’s Sarcoma-Associated Herpesvirus. In: DM Knipe, PM Howley (eds): Fields Virology. Lippincott Williams and Wilkins, Philadelphia, 2803–2833Google Scholar
  89. 89.
    Verschuren EW, Klefstrom J, Evan GI, Jones N (2002) The oncogenic potential of Kaposi’s sarcoma-associated herpesvirus cyclin is exposed by p53 loss in vitro and in vivo. Cancer Cell 2: 229–241CrossRefPubMedGoogle Scholar
  90. 90.
    Verschuren EW, Hodgson JG, Gray JW, Kogan S, Jones N, Evan GI (2004) The role of p53 in suppression of KSHV cyclin-induced lymphomagenesis. Cancer Res 64: 581–589CrossRefPubMedGoogle Scholar
  91. 91.
    Pan H, Zhou F, Gao SJ (2004) Kaposi’s sarcoma-associated herpesvirus induction of chromosome instability in primary human endothelial cells. Cancer Res 64: 4064–4068CrossRefPubMedGoogle Scholar
  92. 92.
    Wu X, Avni D, Chiba T, Yan F, Zhao Q, Lin Y, Heng H, Livingston D (2004) SV40 T antigen interacts with Nbs1 to disrupt DNA replication control. Genes Dev 18: 1305–1316CrossRefPubMedGoogle Scholar
  93. 93.
    Cotsiki M, Lock RL, Cheng Y, Williams GL, Zhao J, Perera D, Freire R, Entwistle A, Golemis EA, Roberts TM et al. (2004) Simian virus 40 large T antigen targets the spindle assembly checkpoint protein Bub1. Proc Natl Acad Sci USA 101: 947–952CrossRefPubMedGoogle Scholar
  94. 94.
    Ricciardiello L, Baglioni M, Giovannini C, Pariali M, Cenacchi G, Ripalti A, Landini MP, Sawa H, Nagashima K, Frisque RJ et al. (2003) Induction of chromosomal instability in colonic cells by the human polyomavirus JC virus. Cancer Res 63: 7256–7262PubMedGoogle Scholar
  95. 95.
    Hollinger FB, Liang TJ (2001) Hepatitis B Virus. In: DM Knipe, PM Howley (eds): Fields Virology. Lippincott Williams and Wilkins, Philadelphia, 2971–3036Google Scholar
  96. 96.
    Forgues M, Difilippantonio MJ, Linke SP, Ried T, Nagashima K, Feden J, Valerie K, Fukasawa K, Wang XW (2003) Involvement of Crm1 in hepatitis B virus X protein-induced aberrant centriole replication and abnormal mitotic spindles. Mol Cell Biol 23: 5282–5292CrossRefPubMedGoogle Scholar
  97. 97.
    Yun C, Cho H, Kim SJ, Lee JH, Park SY, Chan GK (2004) Mitotic aberration coupled with centrosome amplification is induced by hepatitis B virus X oncoprotein via the Ras-mitogen-activated protein/extracellular signal-regulated kinase-mitogen-activated protein pathway. Mol Cancer Res 2: 159–169PubMedGoogle Scholar
  98. 98.
    De Luca A, Mangiacasale R, Severino A, Malquori L, Baldi A, Palena A, Mileo AM, Lavia P, Paggi MG (2003) E1A deregulates the centrosome cycle in a Ran GTPase-dependent manner. Cancer Res 63: 1430–1437PubMedGoogle Scholar
  99. 99.
    Carbone M, Klein G, Gruber J, Wong M (2004) Modern criteria to establish human cancer etiology. Cancer Res 64: 5518–5524CrossRefPubMedGoogle Scholar
  100. 100.
    McDougall JK (2001) “Hit and run” transformation leading to carcinogenesis. Dev Biol (Basel) 106: 77–82Google Scholar
  101. 101.
    Eigen M (2002) Error catastrophe and antiviral strategy. Proc Natl Acad Sci USA 99: 13374–13376CrossRefPubMedGoogle Scholar
  102. 102.
    Vidwans SJ, Wong ML, O’Farrell PH (2003) Anomalous centriole configurations are detected in Drosophila wing disc cells upon Cdk1 inactivation. J Cell Sci 116: 137–143CrossRefPubMedGoogle Scholar
  103. 103.
    Duensing S, Lee BH, Dal Cin P, Münger K (2003) Excessive centrosome abnormalities without ongoing numerical chromosome instability in a Burkitt’s lymphoma. Molecular Cancer 2: 30CrossRefPubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag/Switzerland 2006

Authors and Affiliations

  • Karl Münger
    • 1
  • Hiroyuki Hayakawa
    • 1
  • Christine L. Nguyen
    • 1
  • Nadja V. Melquiot
    • 1
  • Anette Duensing
    • 2
  • Stefan Duensing
    • 2
  1. 1.The Channing LaboratoryBrigham and Women’s HospitalBostonUSA
  2. 2.Molecular Virology ProgramUniversity of Pittsburgh Cancer InstitutePittsburghUSA

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