Khan, Nusrat, Akagi, Keiko, Jiang, Shiming, Dunn, Joe Dan, Jiang, Bo, Xiao, Weihong, O'Hara, Madison P, Shen, Li, Wang, Qi, Mohanty, Vakul, Wang, Jing, Goodwin, Sara, Hutchins, Jamie L, Coombes, Kevin R, Sastry, Jagannadha K, Symer, David E, Gillison, Maura L (May 2025) Human papillomavirus integration induces oncogenic host gene fusions in oropharyngeal cancers. Cancer Discovery. ISSN 2159-8274
Abstract
HPV integration disrupts host genomic structure and expression, but whether these alterations promote cancer development remains unclear. Multiple genomic analyses of oropharyngeal cancers identified several host fusion genes, including recurrent FGFR3-TACC3 fusions, expressed from rearranged genomic loci adjacent to HPV integration sites. Evolutionary modeling implicated integration of virus concatemers into the host genome as a common initiating event in fusion formation. Co-expression of HPV16 E6/E7 and FGFR3-TACC3, but neither alone, was sufficient for tumor development in both xenograft and syngeneic mouse models and led to unique transcriptional programs implicated in carcinogenesis. FGFR3-TACC3 expression decreased the ubiquitination and degradation of E6 and E7, thereby increasing oncoprotein abundance. We conclude that expression of HPV16 oncoproteins and host gene fusions generated from HPV integration sites can be sufficient for cancer development.
| Item Type: | Paper |
|---|---|
| Subjects: | diseases & disorders > cancer diseases & disorders diseases & disorders > viral diseases diseases & disorders > viral diseases > human papillomavirus |
| CSHL Authors: | |
| Communities: | CSHL labs > Goodwin lab |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 14 May 2025 |
| Date Deposited: | 23 Jul 2025 14:23 |
| Last Modified: | 23 Jul 2025 14:23 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/41916 |
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