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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

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...

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Main Authors: Viarisio, Daniele (Author) , Robitaille, Alexis (Author) , Müller-Decker, Karin (Author) , Flechtenmacher, Christa (Author) , Gissmann, Lutz (Author) , Tommasino, Massimo (Author)
Format: Article (Journal)
Language:English
Published: 24 September 2019
In: Virology
Year: 2019, Volume: 538, Pages: 53-60
ISSN:1096-0341
DOI:10.1016/j.virol.2019.09.010
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.virol.2019.09.010
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S0042682219302752
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Author Notes:Daniele Viarisio, Alexis Robitaille, Karin Müller-Decker, Christa Flechtenmacher, Lutz Gissmann, Massimo Tommasino
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Summary: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.
Item Description:Gesehen am 20.04.2020
Physical Description:Online Resource
ISSN:1096-0341
DOI:10.1016/j.virol.2019.09.010

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