Medical Microbiology and Immunology

, Volume 176, Issue 5, pp 245–256 | Cite as

Chromosomal integration sites of human papillomavirus DNA in three cervical cancer cell lines mapped by in situ hybridization

  • A. Mincheva
  • L. Gissmann
  • H. zur Hausen


Metaphase chromosomes of three cervical cancer cell lines (HeLa, CasKi, SiHa) were subjected to in situ hybridizations with the DNA of human papillomaviruses (HPV) types 16 and 18, respectively. Previous studies have demonstrated multiple copies of HPV 18 DNA in HeLa and of HPV 16 DNA in CasKi cells, but only 1–2 HPV 16 copies in cells of the SiHa line. The viral DNA persists in an integrated state (Schwarz et al 1985). Analysis of the integration sites revealed at least 11 chromosomal sites of HPV 16 integration in CasKi cells. SiHa cells contain integrated HPV 16 DNA in the region q21–q31 of chromosome No. 13. In HeLa cells integration of HPV 18 occurred in chromosome No. 8, band q24. Thus, no evidence was obtained for the existence of preferential chromosomal regions for HPV integration. The data indirectly support a trans-acting function of HPV-mediated cell transformation.


Cervical Cancer HeLa Cell Integrate State Cell Transformation Integration Site 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Boshard M, Gissmann L, Ikenberg H, Kleinheinz A, Scheurlen W, zur Hausen H (1984) A new type of papillomavirus DNA, its presence in genital cancer biopsies and in cell lines derived from cervical cancer. Eur mol Biol Org J 3:1151–1157Google Scholar
  2. Dalla-favera R, Bregny M, Erikson J, Patterson D, Gallo R, Croce C (1982) Human c-myc one gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc Natl Acad Sci USA 79:7824–7827Google Scholar
  3. Dürst M, Gissmann L, Ikenberg H, zur Hausen H (1983) A new type of papillomavirus DNA from a cervical carcinoma and its prevalence in genital cancer biopsies from different geographic regions. Proc nat Acad Sci USA 80:3812–3815Google Scholar
  4. Dürst M, Kleinheinz A, Hotz A, Gissmann L (1985) The physical state of human papillomavirus type 16 DNA in benign and malignant genital tumors. J gen Virol 66:1515–1522Google Scholar
  5. Friedl F, Kimura I, Osato T, Ito Y (1970) Studies on a new human cell line (SiHa) derived from carcinoma of uterus. I. Its establishment and morphology (35091). Proc Soc Exp Biol Med 135:543–545Google Scholar
  6. Gey G, Coffman W, Kubiceck M (1952) Tissue culture studies of the proliferative capacity of cervical carcinoma and normal epithelium. Cancer Res 12:264–265Google Scholar
  7. Miller O, Miller D, Allderdice P, Dev V, Grewal M (1971) Quinacrine fluorescent karyotypes of human diploid and heteroploid cell lines. Cytogenetics 10:338–346Google Scholar
  8. Neel B, Jhanwar R, Chaganti S, Hayward W (1982) Two human c-onc gene are located on the long arm of chromosome 8. Proc Natl Acad Sci USA 79:7842–7846Google Scholar
  9. Pater MM, Pater A (1985) Human papillomavirus types 16 and 18 sequences in carcinoma cell lines of the cervix. Virology. 145:313–318Google Scholar
  10. Pattilo R, Hussa R, Story M, Ruckert A, Shalaby M, Nattingly R (1977) Tumor antigen and human chorionic Gonadotropin in CaSki cells: a new epidermoid cervical cancer cell line. Science 16:1456–1458Google Scholar
  11. Rappold G, Cremer T, Cremer C, Back W, Bogenberger J, Cooke H (1984) Chromosome assignment of two cloned DNA probes hybridizing predominantly to human sex chromosomes. Hum Genet 65:257–261Google Scholar
  12. Riou G, Barrois M, Tordjman J, Dutronquay V, Orth G (1984) Presence de genomes de papillomavirus et amplification des oncogenes c-myc et c-Ha-ras dans des cancers envahissants du col de l'uterus. C R Acad Sc Paris 299:575–580Google Scholar
  13. Schneider-Gädicke A, Schwarz E (1986) Different human cervical carcinoma cell lines show similar transcription patterns of human papillomavirus type 18 early genes. EMBO J 5:2285–2292Google Scholar
  14. Schwarz E, Freese UK, Gissmann L, Mayer W, Roggenbuck B, Stremlau A, zur Hausen H (1985) Structure and transcription of human papillomavirus sequences in cervical carcinoma cells. Nature 314:111–114Google Scholar
  15. Seedorf K, Oltersdorf T, Krämmer G, Röwekamp W (1987) Identification of early proteins of the human papilloma viruses type 16 (HPV 16) and type 18 (HPV 18), in cervical carcinoma cells. EMBO J (in press)Google Scholar
  16. Smotkin D, Wettstein FO (1986) Transcription of HPV 16 early genes in a cervical cancer-derived cell line and identification of the E7 protein. Proc Natl Acad Sci 83:4680–4684Google Scholar
  17. Standing Committee on Human Cytogenetic Nomenclature (1978) Cytogent Cell Genet 21:309–404Google Scholar
  18. Sumner A, Evans H, Buckland R (1971) New technique for distinguishing between human chromosomes. Nature 232:31–32Google Scholar
  19. Taub R, Kirsch I, Morton C, Lenior G, Swan D, Tronick S, Aaronson S, Leder P (1982) Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells. Proc Natl Acad Sci USA 79:7837–7841Google Scholar
  20. Topp W, Lane D, Pollack R (1980) Transformation by simian virus 40 and polyoma virus. In: J. Tooze (ed) DNA tumor viruses. Cold Spring Harbor Laboratory, pp 205–296Google Scholar
  21. Wang H, Fedoroff S (1972) Banding in human chromosomes treated with trypsin. Nature. 235:52–54Google Scholar
  22. Yee C, Krishnan-Hewlett I, Baker C, Schlegel R, Howley P (1985) Presence and expression of human papillomavirus sequences in human cervical carcinoma cell lines. A J Pathol 119:361–366Google Scholar
  23. Yunis J, Sawyer J, Ball D (1978) Characterization of banding patterns of metaphase-prophase G-banded chromosomes and their use in gene mapping. Cytogenet Cell Genet 22:679–683Google Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • A. Mincheva
    • 1
  • L. Gissmann
    • 1
  • H. zur Hausen
    • 1
  1. 1.Deutsches Krebsforschungszentrum, Institut für VirusforschungHeidelbergFederal Republic of Germany

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