126601 Journal Article.pdf (3.44 MB)
The origins and vulnerabilities of two transmissible cancers in Tasmanian devils
journal contribution
posted on 2023-05-19, 18:55 authored by 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, Ruth PyeRuth Pye, Tubio, JMC, Siddle, HVT, Sukhwinder SohalSukhwinder Sohal, Gregory WoodsGregory Woods, McDermott, U, Yang, F, Garnett, MJ, Ning, Z, Murchison, EPTransmissible 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.
History
Publication title
Cancer CellVolume
33Issue
4Article number
e15Number
e15Pagination
607-619ISSN
1535-6108Department/School
School of Health SciencesPublisher
Cell PressPlace of publication
1100 Massachusetts Ave, Cambridge, USA, Ma, 02138Rights statement
Copyright 2018 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) http://creativecommons.org/licenses/by/4.0/Repository Status
- Open