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Δευτέρα 9 Απριλίου 2018

The Origins and Vulnerabilities of Two Transmissible Cancers in Tasmanian Devils

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Maximilian R. Stammnitz, Tim H.H. Coorens, Kevin C. Gori, Dane Hayes, Beiyuan Fu, Jinhong Wang, Daniel E. Martin-Herranz, Ludmil B. Alexandrov, Adrian Baez-Ortega, Syd Barthorpe, Alexandra Beck, Francesca Giordano, Graeme W. Knowles, Young Mi Kwon, George Hall, Stacey Price, Ruth J. Pye, Jose M.C. Tubio, Hannah V.T. Siddle, Sukhwinder Singh Sohal, Gregory M. Woods, Ultan McDermott, Fengtang Yang, Mathew J. Garnett, Zemin Ning, Elizabeth P. Murchison
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.

Graphical abstract

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Teaser

Stammnitz et al. show that the two transmissible cancer clones that affect Tasmanian devils are very similar in their tissues-of-origin, mutational patterns and driver gene candidates. Importantly, these cancers are both highly sensitive to inhibitors of some receptor tyrosine kinases as well as to inhibitors of DNA repair.


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