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Cancer susceptibility of beta HPV49 E6 and E7 transgenic mice to 4-nitroquinoline 1-oxide treatment correlates with mutational signatures of tobacco exposure.

Authors
  • Viarisio, Daniele1
  • Robitaille, Alexis2
  • Müller-Decker, Karin1
  • Flechtenmacher, Christa3
  • Gissmann, Lutz4
  • Tommasino, Massimo5
  • 1 Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. , (Germany)
  • 2 International Agency for Research on Cancer (IARC), World Health Organization, 150 Cours Albert Thomas, 69372, Lyon Cedex 08, France. , (France)
  • 3 Department of Pathology, University Hospital of Heidelberg, Im Neuenheimer Feld 220, 69120, Heidelberg, Germany. , (Germany)
  • 4 Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany; Department of Botany and Microbiology (honorary MMember), King Saud University, Riyadh, Saudi Arabia. , (Germany)
  • 5 International Agency for Research on Cancer (IARC), World Health Organization, 150 Cours Albert Thomas, 69372, Lyon Cedex 08, France. Electronic address: [email protected] , (France)
Type
Published Article
Journal
Virology
Publisher
Elsevier
Publication Date
Dec 01, 2019
Volume
538
Pages
53–60
Identifiers
DOI: 10.1016/j.virol.2019.09.010
PMID: 31569015
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

We have previously showed that a transgenic (Tg) mouse model with cytokeratin 14 promoter (K14)-driven expression of E6 and E7 from beta-3 HPV49 in the basal layer of the epidermis and of the mucosal epithelia of the digestive tract (K14 HPV49 E6/E7 Tg mice) are highly susceptible to upper digestive tract carcinogenesis upon exposure to 4-nitroquinoline 1-oxide (4NQO). Using whole-exome sequencing, we show that in K14 HPV49 E6/E7 Tg mice, development of 4NQO-induced cancers tightly correlates with the accumulation of somatic mutations in cancer-related genes. The mutational signature in 4NQO-treated mice was similar to the signature observed in humans exposed to tobacco smoking and tobacco chewing. Similar results were obtained with K14 Tg animals expressing mucosal high-risk HPV16 E6 and E7 oncogenes. Thus, beta-3 HPV49 share some functional similarities with HPV16 in Tg animals. Copyright © 2019. Published by Elsevier Inc.

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