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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.

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Authors

Gayle K. McEwen

David E. Alquezar-Planas

Anisha Dayaram

Amber Gillett

NIGEL MONGAN nigel.mongan@nottingham.ac.uk
Associate Pro-Vice Chancellorglobal Engagement

Keith J. Chappell

Joerg Henning

Milton Tan

Peter Timms

Paul R. Young

Alfred L. Roca

Alex D. Greenwood



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., …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

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