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Publication : HPV E2, E4, E5 drive alternative carcinogenic pathways in HPV positive cancers.

First Author  Ren S Year  2020
Journal  Oncogene Volume  39
Issue  40 Pages  6327-6339
PubMed ID  32848210 Mgi Jnum  J:296227
Mgi Id  MGI:6460160 Doi  10.1038/s41388-020-01431-8
Citation  Ren S, et al. (2020) HPV E2, E4, E5 drive alternative carcinogenic pathways in HPV positive cancers. Oncogene 39(40):6327-6339
abstractText  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.
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