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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 pattern...

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Autores principales: 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, Murchison, Elizabeth P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896245/
https://www.ncbi.nlm.nih.gov/pubmed/29634948
http://dx.doi.org/10.1016/j.ccell.2018.03.013
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author 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
Murchison, Elizabeth P.
author_facet 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
Murchison, Elizabeth P.
author_sort Stammnitz, Maximilian R.
collection PubMed
description 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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spelling pubmed-58962452018-04-13 The Origins and Vulnerabilities of Two Transmissible Cancers in Tasmanian Devils 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 Murchison, Elizabeth P. Cancer Cell Article 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. Cell Press 2018-04-09 /pmc/articles/PMC5896245/ /pubmed/29634948 http://dx.doi.org/10.1016/j.ccell.2018.03.013 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
Murchison, Elizabeth P.
The Origins and Vulnerabilities of Two Transmissible Cancers in Tasmanian Devils
title The Origins and Vulnerabilities of Two Transmissible Cancers in Tasmanian Devils
title_full The Origins and Vulnerabilities of Two Transmissible Cancers in Tasmanian Devils
title_fullStr The Origins and Vulnerabilities of Two Transmissible Cancers in Tasmanian Devils
title_full_unstemmed The Origins and Vulnerabilities of Two Transmissible Cancers in Tasmanian Devils
title_short The Origins and Vulnerabilities of Two Transmissible Cancers in Tasmanian Devils
title_sort origins and vulnerabilities of two transmissible cancers in tasmanian devils
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896245/
https://www.ncbi.nlm.nih.gov/pubmed/29634948
http://dx.doi.org/10.1016/j.ccell.2018.03.013
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