Olthof, Nadine C., Speel, Ernst-Jan M., Kolligs, Jutta, Haesevoets, Annick, Henfling, Mieke, Ramaekers, Frans C. S., Preuss, Simon F., Drebber, Uta, Wieland, Ulrike, Silling, Steffi, Lam, Wan L., Vucic, Emily A., Kremer, Bernd, Klussmann, Jens-P. and Huebbers, Christian U. (2014). Comprehensive Analysis of HPV16 Integration in OSCC Reveals No Significant Impact of Physical Status on Viral Oncogene and Virally Disrupted Human Gene Expression. PLoS One, 9 (2). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Infection with high-risk human papillomavirus (HPV) type 16 is an independent risk factor for the development of oropharyngeal squamous cell carcinomas (OSCC). However, it is unclear whether viral integration is an essential hallmark in the carcinogenic process of OSCC and whether HPV integration correlates with the level of viral gene transcription and influences the expression of disrupted host genes. We analyzed 75 patients with OSCC. HPV16-positivity was proven by p16(INK4A) immunohistochemistry, PCR and FISH. Viral integration was examined using DIPS-as well as APOT-PCR. Viral E2, E6 and E7 gene expression levels were quantified by quantitative reverse transcriptase (RT-q) PCR. Expression levels of 7 human genes disrupted by the virus were extracted from mRNA expression profiling data of 32 OSCCs. Viral copy numbers were assessed by qPCR in 73 tumors. We identified 37 HPV16-human fusion products indicating viral integration in 29 (39%) OSCC. In the remaining tumors (61%) only episome-derived PCR products were detected. When comparing OSCC with or without an integration-derived fusion product, we did not find significant differences in the mean RNA expression of viral genes E2, E6 and E7 or the viral copy numbers per cell, nor did the RNA expression of the HPV-disrupted genes differ from either group of OSCC. In conclusion, our data do not support the hypothesis that integration affects the levels of viral and/or HPV-disrupted human gene transcripts. Thus constitutive, rather than a high level, of expression of oncogene transcripts appears to be required in HPV-related OSCC.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Olthof, Nadine C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Speel, Ernst-Jan M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kolligs, JuttaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haesevoets, AnnickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Henfling, MiekeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ramaekers, Frans C. S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Preuss, Simon F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drebber, UtaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wieland, UlrikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Silling, SteffiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lam, Wan L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vucic, Emily A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kremer, BerndUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klussmann, Jens-P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huebbers, Christian U.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-445714
DOI: 10.1371/journal.pone.0088718
Journal or Publication Title: PLoS One
Volume: 9
Number: 2
Date: 2014
Publisher: PUBLIC LIBRARY SCIENCE
Place of Publication: SAN FRANCISCO
ISSN: 1932-6203
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
HUMAN-PAPILLOMAVIRUS TYPE-16; SQUAMOUS-CELL CARCINOMAS; HUMAN-PAPILLOMAVIRUS-16 DNA; CERVICAL-CANCER; IN-SITU; HEAD; E6; PREVALENCE; LESIONS; GENOMEMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/44571

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