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The origins and vulnerabilities of two transmissible cancers in Tasmanian devils

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Stammnitz, MR, Coorens, THH, Gori, KC, Hayes, DA, Fu, B, Wang, J, Martin-Herranz, DE, Alexandrov, LB, Baez-Ortega, A, Barthorpe, S, Beck, A, Giordano, F, Knowles, GW, Kwon, YM, Hall, G, Price, S, Pye, R, Tubio, JMC, Siddle, HVT, Sohal, SS ORCID: 0000-0001-9627-6498, Woods, GM ORCID: 0000-0001-8421-7917, McDermott, U, Yang, F, Garnett, MJ, Ning, Z and Murchison, EP 2018 , 'The origins and vulnerabilities of two transmissible cancers in Tasmanian devils' , Cancer Cell, vol. 33, no. 4 , pp. 607-619 , doi: 10.1016/j.ccell.2018.03.013.

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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.

Item Type: Article
Authors/Creators:Stammnitz, MR and Coorens, THH and Gori, KC and Hayes, DA and Fu, B and Wang, J and Martin-Herranz, DE and Alexandrov, LB and Baez-Ortega, A and Barthorpe, S and Beck, A and Giordano, F and Knowles, GW and Kwon, YM and Hall, G and Price, S and Pye, R and Tubio, JMC and Siddle, HVT and Sohal, SS and Woods, GM and McDermott, U and Yang, F and Garnett, MJ and Ning, Z and Murchison, EP
Keywords: Tasmanian devils, cancer, cancer evolution, cancer genomics, conservation, contagious cancer, drug screening; marsupials, transmissible cancer
Journal or Publication Title: Cancer Cell
Publisher: Cell Press
ISSN: 1535-6108
DOI / ID Number: 10.1016/j.ccell.2018.03.013
Copyright Information:

Copyright 2018 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) http://creativecommons.org/licenses/by/4.0/

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