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Papillomavirus Sequences Integrate near Cellular Oncogenes in Some Cervical Carcinomas

The chromosomal locations of cellular sequences flanking integrated papillomavirus DNA in four cervical carcinoma cell lines and a primary cervical carcinoma have been determined. The two human papillomavirus (HPV) 16 flanking sequences derived from the tumor were localized to chromosome regions 20p...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1987-02, Vol.84 (4), p.1070-1074
Main Authors: Dürst, Matthias, Croce, Carlo M., Gissmann, Lutz, Schwarz, Elisabeth, Huebner, Kay
Format: Article
Language:English
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Summary:The chromosomal locations of cellular sequences flanking integrated papillomavirus DNA in four cervical carcinoma cell lines and a primary cervical carcinoma have been determined. The two human papillomavirus (HPV) 16 flanking sequences derived from the tumor were localized to chromosome regions 20pter→ 20q13 and 3p25→ 3qter, regions that also contain the protooncogenes c-src-1 and c-raf-1, respectively. The HPV 16 integration site in the SiHa cervical carcinoma-derived cell line is in chromosome region 13q14→ 13q32. The HPV 18 integration site in SW756 cervical carcinoma cells is in chromosome 12 but is not closely linked to the Ki-ras2 gene. Finally, in two cervical carcinoma cell lines, HeLa and C4-I, HPV 18 DNA is integrated in chromosome 8, 5′ of the c-myc gene. The HeLa HPV 18 integration site is within 40 kilobases 5′ of the c-myc gene, inside the HL60 amplification unit surrounding and including the c-myc gene. Additionally, steady-state levels of c-myc mRNA are elevated in HeLa and C4-I cells relative to other cervical carcinoma cell lines. Thus, in at least some genital tumors, cis-activation of cellular oncogenes by HPV may be involved in malignant transformation of cervical cells.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.84.4.1070