Integrated Human Papillomavirus Type 16 and Loss of Heterozygosity at 11q22 and 18q21 in an Oral Carcinoma and Its Derivative Cell Line

Renske D.M. Steenbergen, Jan M.M. Walboomers, Chris J.L.M. Meijer, Peter J.F. Snijders, Mario A.J.A. Hermsen, Hans Joenje, Fré Arwert

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

A human papillomavirus (HPV) type 16 containing oral squamous cell carcinoma cell line 93VU147T at early passage was demonstrated to match its primary tumor with regard to HPV status and loss of heterozygosity at loci potentially involved in HPV-mediated carcinogenesis. DNA in situ hybridization of the cell line and the primary tumor revealed the presence of HPV 16 DNA clonally associated with the neoplastic cells. One- and two-dimensional Southern blot hybridization suggested HPV 16 to be integrated in the host genome at over hundred copies/cell. An identical restriction enzyme profile was observed for the tumor and the cell line. Viral DNA integration was confirmed by fluorescence in situ hybridization on metaphase spreads of the cell line, which revealed six stained loci comprising one at 15q14-15 and five at cytogenetically unidentifiable chromosomes. In addition, the tumor and the cell line displayed mRNA expression of the E6/E7 region encoding the viral oncoproteins, as determined by reverse transcription-PCR. Northern blot analysis of the cell line revealed three major and three minor transcripts harboring E67E7 sequences. Both the primary tumor and cell line showed loss of heterozygosity at the 11q22 (D11S35) and 18q21 (DCC) loci. These data support a role for HPV 16 in the development of a subset of oral cancers, presumably in concert with loss of function of tumor suppressor genes at 11q and 18q.

Original languageEnglish
Pages (from-to)5465-5471
Number of pages7
JournalCancer Research
Volume55
Issue number22
Publication statusPublished - 15 Nov 1995

Cite this

Steenbergen, R. D. M., Walboomers, J. M. M., Meijer, C. J. L. M., Snijders, P. J. F., Hermsen, M. A. J. A., Joenje, H., & Arwert, F. (1995). Integrated Human Papillomavirus Type 16 and Loss of Heterozygosity at 11q22 and 18q21 in an Oral Carcinoma and Its Derivative Cell Line. Cancer Research, 55(22), 5465-5471.