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  • Oncogenomics
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Preferential integration of human papillomavirus type 18 near the c-myc locus in cervical carcinoma

Oncogene volume 22, pages 7233–7242 (2003)Cite this article

Abstract

The development of cervical cancer is highly associated with human papillomavirus (HPV) infection. Greater than 99% of all cervical tumors contain HPV DNA. Integration of high-risk HPV has been temporally associated with the acquisition of a malignant phenotype. Recent work from our lab has shown that HPV16, the most common high-risk HPV associated with cervical carcinoma, preferentially integrates at loci containing human common fragile sites (CFSs). CFSs are regions of genomic instability that have also been associated with deletions, translocations, and gene amplification during cancer development. The current work shows that HPV18, the second most prevalent high-risk HPV type found in cervical tumors, preferentially targets the CFSs. We identified 27 unique HPV18 integrations in cervical tumors, of which 63% (P<0.001) occur in CFSs. However, the distribution of HPV18 integrations found were profoundly different from those found for HPV16. Specifically, 30% of all HPV18 integrations occurred within the chromosomal band 8q24 near the c-myc proto-oncogene. None of the HPV16 integrations occurred in this region. Previous low-resolution mapping suggested that c-myc may be a target of HPV integration. Our data at nucleotide resolution confirm that in HPV18-positive cervical tumors, the region surrounding c-myc is indeed a hot spot of viral integration. These results demonstrate that CFSs are preferred sites of integration for HPV18 in cervical tumors. In addition, we have identified multiple cellular genes that have been disrupted by HPV18 integration in cervical tumors. Our results suggest that the sites of HPV18 integration are nonrandom and may play an important role in the development of cervical tumors.

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Acknowledgements

We thank Gert Jan Fleuren and Ed Schuuring for their contributions to this paper. This study was conducted as a part of MJF's doctoral thesis requirements in the Mayo Graduate School. DIS was supported by NCI Grant CA 48031. AATPB was financially supported by the Vanderes Foundation, Leiden, The Netherlands.

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Authors and Affiliations

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

    Matthew J Ferber & Erik C Thorland

  2. Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, 2333AL, The Netherlands

    Antoinette ATP Brink & Anton K Rapp

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

    Leslie A Phillips & David I Smith

  4. Department of Obstetrics and Gynaecology, Mayo Clinic, Rochester, 55905, MN, USA

    Renee McGovern & Bobbie S Gostout

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

    Tak Hong Cheung, Tong Kwok Hung Chung & Wong Yick Fu

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  1. Matthew J Ferber
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Correspondence to David I Smith.

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Ferber, M., Thorland, E., Brink, A. et al. Preferential integration of human papillomavirus type 18 near the c-myc locus in cervical carcinoma. Oncogene 22, 7233–7242 (2003). https://doi.org/10.1038/sj.onc.1207006

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