Retroviral integrations contribute to elevated host cancer rates during germline invasion
| Autor: | Amber Gillett, Anisha Dayaram, Milton Tan, Nigel P. Mongan, Gayle K. McEwen, Joerg Henning, Alfred L. Roca, Paul R. Young, David E. Alquezar-Planas, Alex D. Greenwood, Keith J. Chappell, Rachael E. Tarlinton, Peter Timms |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Retrovirus Cancer genetics Cancer genomics Evolutionary biology Science bcl-X Protein Endogenous retrovirus General Physics and Astronomy Genome Germline Article General Biochemistry Genetics and Molecular Biology Evolution Molecular 03 medical and health sciences 0302 clinical medicine Phascolarctos cinereus biology.animal Neoplasms medicine Animals Humans Gene Genetics Multidisciplinary biology Oncogene Genome Human Endogenous Retroviruses Cancer General Chemistry biology.organism_classification medicine.disease Gene Expression Regulation Neoplastic Repressor Proteins 030104 developmental biology Germ Cells Retroviridae 030220 oncology & carcinogenesis Koala retrovirus Gammaretrovirus Phascolarctidae Retroviridae Infections |
| Zdroj: | Nature Communications, 12(1):1316 Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-13 (2021) |
| ISSN: | 2041-1723 |
| Popis: | 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 high cancer prevalence. 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. Koalas are susceptible to neoplasms, which are related to infection with the Koala retrovirus. Here, the authors use DNA sequencing to show that the retroviral insertion sites cluster near known cancer genes and demonstrate a high mutational load associated with the germline invasion of the virus. |
| Databáze: | OpenAIRE |
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