Retroviral integrations contribute to elevated host cancer rates during germline invasion

Gayle K. McEwen, David E. Alquezar-Planas, Anisha Dayaram, Amber Gillett, Rachael Tarlinton, Nigel Mongan, Keith J. Chappell, Joerg Henning, Milton Tan, Peter Timms, Paul R. Young, Alfred L. Roca (+1 others)
2021 Nature Communications  
AbstractRepeated 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 high cancer prevalence. We characterise
more » ... RV 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.
doi:10.1038/s41467-021-21612-7 pmid:33637755 fatcat:w5eyhtrzrrfetcp5ab4x6syqgu