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

M. J. Ferber, D. P. Montoya, C. Yu, I. Aderca, A. McGee, E. C. Thorland, D. M. Nagorney, B. S. Gostout, L. J. Burgart, L. Boix, J. Bruix, B. J. McMahon, T. H. Cheung, T. K.H. Chung, Y. F. Wong, D. I. Smith, L. R. Roberts

Research output: Contribution to journalArticle

155 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3813-3820
Number of pages8
JournalOncogene
Volume22
Issue number24
DOIs
StatePublished - Jun 12 2003

Keywords

  • Cervical cancer
  • Hepatitis B virus
  • Hepatocellular carcinoma
  • Human papillomavirus
  • Telomerase reverse transcriptase
  • Viral integration

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Ferber, M. J., Montoya, D. P., Yu, C., Aderca, I., McGee, A., Thorland, E. C., Nagorney, D. M., Gostout, B. S., Burgart, L. J., Boix, L., Bruix, J., McMahon, B. J., Cheung, T. H., Chung, T. K. H., Wong, Y. F., Smith, D. I., & Roberts, L. R. (2003). 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(24), 3813-3820. https://doi.org/10.1038/sj.onc.1206528