Abstract B17: Functional characterization of HPV-human fusion transcripts in oropharyngeal cancer

Human papillomavirus (HPV) genomic integration is frequently seen in oropharyngeal squamous cell carcinoma (OPSCC). Integration into cellular genes can cause the generation of HPV-host fusion transcripts, which have been associated with worse survival in OPSCC patients, but their functional consequences are unknown, as HPV alone is capable of transformation. The forced expression of fusion transcripts versus HPV transcripts in spontaneously immortalized human oral keratinocytes (NOKSI) could demonstrate their effects on cell behavior. Our research focuses on characterizing HPV integration sites and fusion transcripts in cell lines and tumors, followed by in vitro analysis of fusion transcript function. By Detection of Integrated Papillomavirus Sequences (DIPS-PCR) and RT-PCR, we have identified integration events and fusion transcripts in a subset of samples in both intergenic and genic regions of the genome. We began our analysis with two fusion transcripts, one reading from HPV16 E6*-E7-E1 into the tumor suppressor gene TP63 from UM-SCC-47 and the other reading from HPV16 E6*-E4 into the solute carrier gene SLC47A2 from UM-SCC-104. The full fusion transcripts and associated controls were cloned into lentiviral vectors, and stable keratinocyte populations expressing these transcripts were selected. These cultures were subjected to proliferation, migration, and invasion assays. Subsequent in-depth molecular characterization and in vivo studies will help clarify their effects on cancer formation and metastasis. These studies will advance our understanding of how fusion transcripts lead to worse patient survival and help develop new therapies for these patients.

Citation Format: Lisa M. Pinatti, Heather M. Walline, Thomas E. Carey. Functional characterization of HPV-human fusion transcripts in oropharyngeal cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B17.