13. HPV forms chimeric virus-human transcripts that affect host gene expression in cervical tumors

Kay Jayachandran


Kay Jayachandrana, Rashmi Pillaib, Matthew Inkmana, Fiona Ruiza, Jace Webstera, Julie Schwarza, Christopher Mahera, Jin Zhanga

aWashington University School of Medicine, St. Louis, MO, United States; bAgilent Technologies, San Diego, CA, United States

BACKGROUND: Cervical cancer is a common gynecological tumor, primarily caused by HPV infection. Integration of HPV into the human genome allows aberrant expression of HPV oncogenes E6 and E7. However, whether HPV-human gene fusions arise from these events and their effects on human gene partners are less studied.

METHODS: Using TCGA cervical cancer RNA-seq data (N=304) and 3 cell lines, we modified and applied our human gene fusion discovery tool, INTEGRATE, to detect chimeric virus-host transcripts, followed by manual inspection for expressed HPV-human gene fusions using NCBI’s BLAST. HPV-human fusion junctions were validated using qRT-PCR, and their effects on human gene partners were characterized.

RESULTS: Greater than 30% of samples contain at least 1 HPV-human transcript with a clear exon-to-exon structure. 22% of these HPV-human fusions share the same human gene partner with at least 1 human-human gene fusion in other samples. qRT-PCR validated HPV-human fusions in the cell lines, including a chimeric transcript with lincRNA LINC00393, also found in 2 TCGA samples. Notably, HPV fused recurrently to the PVT1 and CASC8 lincRNAs in the 8q24 region, which upregulated MYC gene expression. For samples involving multiple detected HPV-human breakpoints in the same gene, we propose the transcribed RNA exhibits a looping structure previously observed in DNA.

CONCLUSION: We showed that HPV-human gene fusion transcripts can be detected using RNA-seq data, which affect human cancer gene expression.