Abstract 3784: Role of HPV-human fusion transcripts in oropharyngeal cancer development

Abstract

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 a fusion transcript reading from HPV16 E6-E7-E1 into the tumor suppressor gene TP63 from UM-SCC-47. The full fusion transcript and the HPV portion only were cloned into lentiviral vectors, and stable NOKSI populations expressing these transcripts were selected. These cultures, as well as control 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 Pinatti, Heather Walline, Thomas Carey. Role of HPV-human fusion transcripts in oropharyngeal cancer development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3784.