Abstract:
:The dominant paradigm for HPV carcinogenesis includes integration into the host genome followed by expression of E6 and E7 (E6/E7). We explored an alternative carcinogenic pathway characterized by episomal E2, E4, and E5 (E2/E4/E5) expression. Half of HPV positive cervical and pharyngeal cancers comprised a subtype with increase in expression of E2/E4/E5, as well as association with lack of integration into the host genome. Models of the E2/E4/E5 carcinogenesis show p53 dependent enhanced proliferation in vitro, as well as increased susceptibility to induction of cancer in vivo. Whole genomic expression analysis of the E2/E4/E5 pharyngeal cancer subtype is defined by activation of the fibroblast growth factor receptor (FGFR) pathway and this subtype is susceptible to combination FGFR and mTOR inhibition, with implications for targeted therapy.
journal_name
Oncogenejournal_title
Oncogeneauthors
Ren S,Gaykalova DA,Guo T,Favorov AV,Fertig EJ,Tamayo P,Callejas-Valera JL,Allevato M,Gilardi M,Santos J,Fukusumi T,Sakai A,Ando M,Sadat S,Liu C,Xu G,Fisch KM,Wang Z,Molinolo AA,Gutkind JS,Ideker T,Koch WM,Calidoi
10.1038/s41388-020-01431-8subject
Has Abstractpub_date
2020-10-01 00:00:00pages
6327-6339issue
40eissn
0950-9232issn
1476-5594pii
10.1038/s41388-020-01431-8journal_volume
39pub_type
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