Retroviral integrations contribute to elevated host cancer rates during germline invasion

McEwen, Gayle K.; Alquezar-Planas, David E.; Dayaram, Anisha; Gillett, Amber; Tarlinton, Rachael; Mongan, Nigel; Chappell, Keith J.; Henning, Joerg; Tan, Milton; Timms, Peter; Young, Paul R.; Roca, Alfred L.; Greenwood, Alex D.

Abstract

© 2021, The Author(s). Repeated retroviral infections of vertebrate germlines have made endogenous retroviruses ubiquitous features of mammalian genomes. However, millions of years of evolution obscure many of the immediate repercussions of retroviral endogenisation on host health. Here we examine retroviral endogenisation during its earliest stages in the koala (Phascolarctos cinereus), a species undergoing germline invasion by koala retrovirus (KoRV) and affected by highcancerprevalence. We characterise KoRV integration sites (IS) in tumour and healthy tissues from 10 koalas, detecting 1002 unique IS, with hotspots of integration occurring in the vicinity of known cancer genes. We find that tumours accumulate novel IS, with proximate genes over-represented for cancer associations. We detect dysregulation of genes containing IS and identify a highly-expressed transduced oncogene. Our data provide insights into the tremendous mutational load suffered by the host during active retroviral germline invasion, a process repeatedly experienced and overcome during the evolution of vertebrate lineages.

Citation

McEwen, G. K., Alquezar-Planas, D. E., Dayaram, A., Gillett, A., Tarlinton, R., Mongan, N., Chappell, K. J., Henning, J., Tan, M., Timms, P., Young, P. R., Roca, A. L., & Greenwood, A. D. (2021). Retroviral integrations contribute to elevated host cancer rates during germline invasion. Nature Communications, 12(1), https://doi.org/10.1038/s41467-021-21612-7

• Journal Article Type: Article
• Acceptance Date: Feb 1, 2021
• Online Publication Date: Feb 26, 2021
• Publication Date: Feb 26, 2021
• Deposit Date: Feb 26, 2021
• Publicly Available Date: Feb 26, 2021
• Journal: Nature Communications
• Electronic ISSN: 2041-1723
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 12
• Issue: 1
• DOI: https://doi.org/10.1038/s41467-021-21612-7
• Keywords: General Biochemistry, Genetics and Molecular Biology; General Physics and Astronomy; General Chemistry
• Public URL: https://nottingham-repository.worktribe.com/output/5352486
• Publisher URL: https://www.nature.com/articles/s41467-021-21612-7
• Additional Information: McEwen, G.K., Alquezar-Planas, D.E., Dayaram, A. et al. Retroviral integrations contribute to elevated host cancer rates during germline invasion. Nat Commun 12, 1316 (2021). https://doi.org/10.1038/s41467-021-21612-7