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  • Oncogenomics
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Integrations of the hepatitis B virus (HBV) and human papillomavirus (HPV) into the human telomerase reverse transcriptase (hTERT) gene in liver and cervical cancers

Oncogene volume 22, pages 3813–3820 (2003)Cite this article

Abstract

Chronic infections with the hepatitis B virus (HBV) and high-risk human papillomaviruses (HPVs) are important risk factors for hepatocellular carcinoma (HCC) and cervical cancer (CC), respectively. HBV and HPV are DNA viruses that almost invariably integrate into the host genome in invasive tumors. The viral integration sites occur throughout the genome, leading to the presumption that there are no preferred sites of integration. A number of viral integrations have been shown to occur within the vicinity of important cancer-related genes. In studies of HBV-induced HCC and HPV-induced CC, we have identified two HBV and three HPV integrations into the human telomerase reverse transcriptase (hTERT) gene. Detailed characterization of the integrations revealed that four integrations occurred within the hTERT promoter and upstream region and the fifth integration occurred in intron 3 of the hTERT gene. None of the integrations altered the hTERT coding sequence and all resulted in juxtaposition of viral enhancers near hTERT, with potential activation of hTERT expression. Our work supports the hypothesis that the sites of oncogenic viral integration are nonrandom and that genes at the sites of viral integration may play important roles in carcinogenesis.

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References

  • Benbrook D, Lernhardt E and Pfahl M . (1988). Nature, 333, 669–672.

  • Berasain C, Patil D, Perara E, Huang SM, Mouly H and Bréchot C . (1998). Oncogene, 16, 1277–1288.

  • Brechot C, Gozuacik D, Murakami Y and Paterlini-Brechot P . (2000). Semin. Cancer Biol., 10, 211–231.

  • Buendia MA . (1992). Semin. Cancer Biol., 3, 309–320.

  • Chami M, Gozuacik D, Saigo K, Capiod T, Falson P, Lecoeur H, Urashima T, Beckmann J, Gougeon ML, Claret M, le Maire M, Brechot C and Paterlini-Brechot P . (2000). Oncogene, 19, 2877–2886.

  • Choo KB, Huang CJ, Chen CM, Han CP and Au LC . (1995). Cancer Lett., 93, 249–253.

  • Dejean A, Bougueleret L, Grzeschik KH and Tiollais P . (1986). Nature, 322, 70–72.

  • Dejean A and de The H . (1990). Mol. Biol. Med., 7, 213–222.

  • Fourel G, Trepo C, Bougueleret L, Henglein B, Ponzetto A, Tiollais P and Buendia MA . (1990). Nature, 347, 294–298.

  • Garcia M, de The H, Tiollais P, Samarut J and Dejean A . (1993). Proc. Natl. Acad. Sci. USA, 90, 89–93.

  • Gozuacik D, Murakami Y, Saigo K, Chami M, Mugnier C, Lagorce D, Okanoue T, Urashima T, Brechot C and Paterlini-Brechot P . (2001). Oncogene, 20, 6233–6240.

  • Horikawa I and Barrett JC . (2001). J. Natl. Cancer Inst., 93, 1171–1173.

  • Horikawa I, Cable PL, Afshari C and Barrett JC . (1999). Cancer Res., 59, 826–830.

  • Hsu T, Moroy T, Etiemble J, Louise A, Trepo C, Tiollais P and Buendia MA . (1988). Cell, 55, 627–635.

  • Jeon S, Allen-Hoffmann BL and Lambert PF . (1995). J. Virol., 69, 2989–2997.

  • Kalantari M, Karlsen F, Kristensen G, Holm R, Hagmar B and Johansson B . (1998). Int. J. Gynecol. Pathol., 17, 146–153.

  • Kekule AS, Lauer U, Meyer M, Caselmann WH, Hofschneider PH and Koshy R . (1990). Nature, 343, 457–461.

  • Kozuka T, Aoki Y, Nakagawa K, Ohtomo K, Yoshikawa H, Matsumoto K, Yoshiike K and Kanda T . (2000). Jpn. J. Cancer Res., 91, 271–279.

  • Leem SH, Londono-Vallejo JA, Kim JH, Bui H, Tubacher E, Solomon G, Park JE, Horikawa I, Kouprina N, Barrett JC and Larionov V . (2002). Oncogene, 21, 769–777.

  • Matsubara K and Tokino T . (1990). Mol. Biol. Med., 7, 243–260.

  • Reuter S, Bartelmann M, Vogt M, Geisen C, Napierski I, Kahn T, Delius H, Lichter P, Weitz S, Korn B and Schwarz E . (1998). EMBO J., 17, 215–222.

  • Sarkar G, Turner RT and Bolander ME . (1993). PCR Methods Appl., 2, 318–322.

  • Sastre-Garau X, Favre M, Couturier J and Orth G . (2000). J. Gen. Virol., 81, 1983–1993.

  • Shera KA, Shera CA and McDougall JK . (2001). J. Virol., 75, 12339–12346.

  • Smola-Hess S, de Silva US, Hadaschik D and Pfister HJ . (2001). J. Gen. Virol., 82, 2335–2339.

  • Steger G and Corbach S . (1997). J. Virol., 71, 50–58.

  • Thorland EC, Myers SL, Gostout BS and Smith DI . (2003). Oncogene, 22, 1225–1237.

  • Thorland EC, Myers SL, Persing DH, Sarkar G, McGovern RM, Gostout BS and Smith DI . (2000). Cancer Res., 60, 5916–5921.

  • Vernon SD, Unger ER, Miller DL, Lee DR and Reeves WC . (1997). Int. J. Cancer, 74, 50–56.

  • Wang J, Chenivesse X, Henglein B and Bréchot C . (1990). Nature, 343, 555–557.

  • Wang J, Zindy F, Chenivesse X, Lamas E, Henglein B and Brechot C . (1992). Oncogene, 7, 1653–1656.

  • Waris G and Siddiqui A . (2002). J. Virol., 76, 2721–2729.

  • Weber KL, Bolander ME and Sarkar G . (1998). BioTechniques, 25, 415–419.

  • Wilke CM, Hall BK, Hoge A, Paradee W, Smith DI and Glover TW . (1996). Hum. Mol. Genet., 5, 187–195.

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Acknowledgements

The secretarial assistance of Kristi Simmons is gratefully acknowledged. This work was supported by grants from the National Institutes of Health (CA82862 to LR Roberts and CA48031 to DI Smith), the Department of Defense (DOD DAMD17-99-1-9504 to DI Smith), the Fraternal Order of Eagles Cancer Fund (to LR Roberts), an Industry Research Scholar Award from the Foundation for Digestive Health and Nutrition (to LR Roberts), a Minority Medical Faculty Development Award from The Robert Wood Johnson Foundation (to LR Roberts), and by the Mayo Foundation.

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Author notes

  1. M J Ferber and D P Montoya: These authors contributed equally to this work

Authors and Affiliations

  1. Division of Experimental Pathology, Mayo Clinic, Rochester, 55905, MN, USA

    M J Ferber, A McGee, E C Thorland & D I Smith

  2. Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, 55905, MN, USA

    M J Ferber

  3. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, 55905, MN, USA

    D P Montoya, C Yu, I Aderca & L R Roberts

  4. Division of Gastroenterologic and General Surgery, Mayo Clinic, Rochester, 55905, MN, USA

    D M Nagorney

  5. Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, 55905, MN, USA

    B S Gostout

  6. Division of Anatomic Pathology, Mayo Clinic, Rochester, 55905, MN, USA

    L J Burgart

  7. BCLC Group Liver Unit, IMD Hospital Clinic, University of Barcelona, Villarroel 170, Barcelona, 08036, Spain

    L Boix & J Bruix

  8. Alaska Native Medical Center, Anchorage, 99508, AK, USA

    B J McMahon

  9. Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, People's Republic of China

    T H Cheung, T K H Chung & Y F Wong

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  1. M J Ferber
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  2. D P Montoya
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  3. C Yu
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  16. D I Smith
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  17. L R Roberts
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Correspondence to L R Roberts.

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Ferber, M., Montoya, D., Yu, C. et al. Integrations of the hepatitis B virus (HBV) and human papillomavirus (HPV) into the human telomerase reverse transcriptase (hTERT) gene in liver and cervical cancers. Oncogene 22, 3813–3820 (2003). https://doi.org/10.1038/sj.onc.1206528

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