Common fragile sites are preferential targets for HPV16 integrations in cervical tumors

Erik C. Thorland, Shannon L. Myers, Bobbie S. Gostout, David I. Smith

Research output: Contribution to journalArticle

186 Scopus citations

Abstract

The development of cervical cancer is highly associated with human papillomavirus (HPV) infection. HPV integration into the genome of infected cervical cells is temporally associated with the acquisition of the malignant phenotype. A relationship between the sites of HPV integration in cervical cancer and the position of the common fragile sites (CFSs) has been observed at both the cytogenetic and molecular levels. To further explore this relationship at the molecular level, we used RS-PCR to rapidly isolate cellular sequences flanking the sites of HPV16 integration in 26 primary cervical tumors. Human bacterial artificial chromosome clones were isolated based on these flanking sequences and used as probes for fluorescence in situ hybridization on aphidicolin-stimulated metaphases. Our data demonstrate that 11/23 HPV16 integrations in cervical tumors occurred within CFSs (P < 0.001). In addition, we show that deletions and complex rearrangements frequently occur in the cellular sequences targeted by the integrations and that integrations cluster in FRA13C (13q22), FRA3B (3p14.2), and FRA17B (17q23). Finally, our data suggest that cellular genes, such as Notch 1, are disrupted by the HPV16 integrations, which may contribute to the malignant phenotype.

Original languageEnglish (US)
Pages (from-to)1225-1237
Number of pages13
JournalOncogene
Volume22
Issue number8
DOIs
StatePublished - Feb 27 2003

Keywords

  • Cervical cancer
  • Common fragile sites
  • Human papillomavirus
  • RS-PCR
  • Viral integration

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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