Transmissible Cancer Group, Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.
Mount Pleasant Laboratories, Tasmanian Department of Primary Industries, Parks, Water and the Environment, Prospect, TAS 7250, Australia; School of Health Sciences, Faculty of Health, University of Tasmania, Launceston, TAS 7248, Australia.
Cancer Cell. 2018 Apr 9;33(4):607-619.e15. doi: 10.1016/j.ccell.2018.03.013.
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.
传染性癌症是通过传染性癌细胞在人群中传播的克隆谱系。尽管在自然界中很少见，但两种面部肿瘤克隆影响塔斯马尼亚恶魔。在这里，我们对这些谱系进行了比较遗传和功能表征。这两种癌症具有相似的突变模式，没有接触外源性诱变剂或病毒的证据。编码 PDGF 受体的基因存在拷贝数增益，并存在于染色体外的双分钟染色体上。药物筛选表明受体酪氨酸激酶起因果作用，并且对 DNA 修复抑制剂敏感。从感染雌性宿主的雄性克隆中丢失 Y 染色体表明免疫编辑。这些结果表明，塔斯马尼亚恶魔可能对传染性癌症具有固有易感性，并提供了一系列用于保护的治疗化合物。
