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The origins and vulnerabilities of two transmissible cancers in Tasmanian devils

The origins and vulnerabilities of two transmissible cancers in Tasmanian devils
The origins and vulnerabilities of two transmissible cancers in Tasmanian devils

Transmissible cancers are clonal lineages that spread through populations via contagious cancer cells. Although rare in nature, two facial tumor clones affect Tasmanian devils. Here we perform comparative genetic and functional characterization of these lineages. The two cancers have similar patterns of mutation and show no evidence of exposure to exogenous mutagens or viruses. Genes encoding PDGF receptors have copy number gains and are present on extrachromosomal double minutes. Drug screening indicates causative roles for receptor tyrosine kinases and sensitivity to inhibitors of DNA repair. Y chromosome loss from a male clone infecting a female host suggests immunoediting. These results imply that Tasmanian devils may have inherent susceptibility to transmissible cancers and present a suite of therapeutic compounds for use in conservation.

Journal Article
1535-6108
607-619.e15
Stammnitz, Maximilian R.
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Coorens, Tim H.H.
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Gori, Kevin C.
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Hayes, Dane
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Fu, Beiyuan
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Wang, Jinhong
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Martin-Herranz, Daniel E.
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Alexandrov, Ludmil B.
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Baez-Ortega, Adrian
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Barthorpe, Syd
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Beck, Alexandra
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Giordano, Francesca
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Knowles, Graeme W.
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Kwon, Young Mi
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Hall, George
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Price, Stacey
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Pye, Ruth J.
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Tubio, Jose M.C.
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Siddle, Hannah V.T.
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Sohal, Sukhwinder Singh
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Woods, Gregory M.
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McDermott, Ultan
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Yang, Fengtang
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Garnett, Mathew J.
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Ning, Zemin
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Murchison, Elizabeth P.
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Stammnitz, Maximilian R.
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Coorens, Tim H.H.
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Gori, Kevin C.
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Hayes, Dane
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Fu, Beiyuan
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Wang, Jinhong
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Martin-Herranz, Daniel E.
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Alexandrov, Ludmil B.
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Baez-Ortega, Adrian
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Barthorpe, Syd
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Beck, Alexandra
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Giordano, Francesca
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Knowles, Graeme W.
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Kwon, Young Mi
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Hall, George
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Price, Stacey
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Pye, Ruth J.
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Tubio, Jose M.C.
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Siddle, Hannah V.T.
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Sohal, Sukhwinder Singh
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Woods, Gregory M.
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McDermott, Ultan
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Yang, Fengtang
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Garnett, Mathew J.
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Ning, Zemin
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Murchison, Elizabeth P.
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Stammnitz, Maximilian R., Coorens, Tim H.H., Gori, Kevin C., Hayes, Dane, Fu, Beiyuan, Wang, Jinhong, Martin-Herranz, Daniel E., Alexandrov, Ludmil B., Baez-Ortega, Adrian, Barthorpe, Syd, Beck, Alexandra, Giordano, Francesca, Knowles, Graeme W., Kwon, Young Mi, Hall, George, Price, Stacey, Pye, Ruth J., Tubio, Jose M.C., Siddle, Hannah V.T., Sohal, Sukhwinder Singh, Woods, Gregory M., McDermott, Ultan, Yang, Fengtang, Garnett, Mathew J., Ning, Zemin and Murchison, Elizabeth P. (2018) The origins and vulnerabilities of two transmissible cancers in Tasmanian devils. Cancer Cell, 33 (4), 607-619.e15. (doi:10.1016/j.ccell.2018.03.013).

Record type: Article

Abstract

Transmissible cancers are clonal lineages that spread through populations via contagious cancer cells. Although rare in nature, two facial tumor clones affect Tasmanian devils. Here we perform comparative genetic and functional characterization of these lineages. The two cancers have similar patterns of mutation and show no evidence of exposure to exogenous mutagens or viruses. Genes encoding PDGF receptors have copy number gains and are present on extrachromosomal double minutes. Drug screening indicates causative roles for receptor tyrosine kinases and sensitivity to inhibitors of DNA repair. Y chromosome loss from a male clone infecting a female host suggests immunoediting. These results imply that Tasmanian devils may have inherent susceptibility to transmissible cancers and present a suite of therapeutic compounds for use in conservation.

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Accepted/In Press date: 11 March 2018
e-pub ahead of print date: 9 April 2018
Published date: 9 April 2018
Keywords: Journal Article
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Identifiers

Local EPrints ID: 421058
URI: http://eprints.soton.ac.uk/id/eprint/421058
DOI: doi:10.1016/j.ccell.2018.03.013
ISSN: 1535-6108
PURE UUID: da08def3-3f4d-4cfc-8f53-be89dc276d57
ORCID for Hannah V.T. Siddle: ORCID iD orcid.org/0000-0003-2906-4385

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Date deposited: 21 May 2018 16:30
Last modified: 16 Mar 2024 04:18

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Contributors

Author: Maximilian R. Stammnitz
Author: Tim H.H. Coorens
Author: Kevin C. Gori
Author: Dane Hayes
Author: Beiyuan Fu
Author: Jinhong Wang
Author: Daniel E. Martin-Herranz
Author: Ludmil B. Alexandrov
Author: Adrian Baez-Ortega
Author: Syd Barthorpe
Author: Alexandra Beck
Author: Francesca Giordano
Author: Graeme W. Knowles
Author: Young Mi Kwon
Author: George Hall
Author: Stacey Price
Author: Ruth J. Pye
Author: Jose M.C. Tubio
Author: Hannah V.T. Siddle ORCID iD
Author: Sukhwinder Singh Sohal
Author: Gregory M. Woods
Author: Ultan McDermott
Author: Fengtang Yang
Author: Mathew J. Garnett
Author: Zemin Ning
Author: Elizabeth P. Murchison

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