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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Biological activity of probable/possible high-risk human papillomavirus types in cervical cancer
International Journal of Cancer, Volume 132, No. 1, Year 2013
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Description
Judging the carcinogenicity of human papillomavirus (HPV) types rarely found in cervical cancer (CxCa) is hindered by lack of studies of their biological activity in cancer tissues. To asses transcriptional activity of HPV types, we have developed ultra-short amplimer, splice-site specific, E6*I mRNA RT-PCR assays for 12 high-risk (HR)-HPV (IARC Group 1) and eight probable/possible high-risk (pHR)-HPV types (IARC Group 2A/B carcinogens). Previously unreported E6*I splice sites of the six pHR-HPV types 26, 53, 67, 70, 73 and 82 were identified by cloning and sequencing. We analyzed 97 formalin-fixed paraffin-embedded (FFPE) Mongolian CxCa biopsies for presence of HPV DNA by two sensitive genotyping assays, for E6*I transcripts of all HR-/pHR-HPV types identified and for expression of HPV surrogate markers p16INK4a, pRb and p53. E6*I of at least one HR-/pHR-HPV was expressed in 94 (98%) of cancer tissues including seven with pHR-HPV types 26, 66, 70 or 82 as single transcribed types. Fifty-eight of E6*I mRNA transcribing cases were analyzable by immunohistochemistry and displayed p16INK4a overexpression in 57 (98%), pRb downregulation in 56 (97%) and p53 downregulation in 36 (62%) tissues. The newly developed E6*I mRNA RT-PCR assays appeared to be highly sensitive method to analyze HPV transcription in FFPE materials. Our finding of viral oncogene transcription of pHR-HPV types 26, 66, 70 and 82 in cervical tumors, in the absence of any other transcriptionally active HR-type and with p16INK4a overexpression and pRb downregulation, may support a reassessment of the carcinogenicity classification of these pHR-HPV types. Copyright © 2012 UICC.
Authors & Co-Authors
Halec, Gordana
Germany, Heidelberg
German Cancer Research Center
Germany, Heidelberg
Universität Heidelberg
Schmitt, Markus
Germany, Heidelberg
German Cancer Research Center
Dondog, Bolormaa
Germany, Heidelberg
German Cancer Research Center
France, Lyon
Centre International de Recherche Sur le Cancer
Sharkhuu, Enkhtuya
Mongolia
National Cancer Centre of Mongolia (nccm)
Wentzensen, Nicolas A.
United States, Rockville
National Cancer Institute Nci
Gheit, Tarik
France, Lyon
Centre International de Recherche Sur le Cancer
Tommasino, Massimo
France, Lyon
Centre International de Recherche Sur le Cancer
Kommoss, Friedrich G.M.
Germany, Mannheim
Referral Center for Gynecopathology
Bosch, Franz X.
Germany, Heidelberg
Universität Heidelberg
Franceschi, Silvia F.
France, Lyon
Centre International de Recherche Sur le Cancer
Clifford, Gary M.
France, Lyon
Centre International de Recherche Sur le Cancer
Gissmann, Lutz Martin
Germany, Heidelberg
German Cancer Research Center
Saudi Arabia, Riyadh
King Saud University
Pawlita, Michael
Germany, Heidelberg
German Cancer Research Center
Statistics
Citations: 125
Authors: 13
Affiliations: 7
Identifiers
Doi:
10.1002/ijc.27605
ISSN:
00207136
e-ISSN:
10970215
Research Areas
Cancer
Genetics And Genomics