Pye Ruth J, Pemberton David, Tovar Cesar, Tubio Jose M C, Dun Karen A, Fox Samantha, Darby Jocelyn, Hayes Dane, Knowles Graeme W, Kreiss Alexandre, Siddle Hannah V T, Swift Kate, Lyons A Bruce, Murchison Elizabeth P, Woods Gregory M
Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7000, Australia;
Save the Tasmanian Devil Program, Tasmanian Department of Primary Industries, Parks, Water and the Environment, Hobart, TAS 7000, Australia;
Proc Natl Acad Sci U S A. 2016 Jan 12;113(2):374-9. doi: 10.1073/pnas.1519691113. Epub 2015 Dec 28.
Clonally transmissible cancers are somatic cell lineages that are spread between individuals via the transfer of living cancer cells. There are only three known naturally occurring transmissible cancers, and these affect dogs, soft-shell clams, and Tasmanian devils, respectively. The Tasmanian devil transmissible facial cancer was first observed in 1996, and is threatening its host species with extinction. Until now, this disease has been consistently associated with a single aneuploid cancer cell lineage that we refer to as DFT1. Here we describe a second transmissible cancer, DFT2, in five devils located in southern Tasmania in 2014 and 2015. DFT2 causes facial tumors that are grossly indistinguishable but histologically distinct from those caused by DFT1. DFT2 bears no detectable cytogenetic similarity to DFT1 and carries a Y chromosome, which contrasts with the female origin of DFT1. DFT2 shows different alleles to both its hosts and DFT1 at microsatellite, structural variant, and major histocompatibility complex (MHC) loci, confirming that it is a second cancer that can be transmitted between devils as an allogeneic, MHC-discordant graft. These findings indicate that Tasmanian devils have spawned at least two distinct transmissible cancer lineages and suggest that transmissible cancers may arise more frequently in nature than previously considered. The discovery of DFT2 presents important challenges for the conservation of Tasmanian devils and raises the possibility that this species is particularly prone to the emergence of transmissible cancers. More generally, our findings highlight the potential for cancer cells to depart from their hosts and become dangerous transmissible pathogens.
克隆可传播性癌症是通过活癌细胞的转移在个体间传播的体细胞谱系。已知的自然发生的可传播性癌症仅有三种,分别影响犬类、软壳蛤和袋獾。袋獾可传播性面部癌症于1996年首次被观察到,正威胁着其宿主物种走向灭绝。到目前为止,这种疾病一直与单一的非整倍体癌细胞谱系相关,我们将其称为DFT1。在此,我们描述了2014年和2015年在塔斯马尼亚岛南部的五只袋獾身上发现的第二种可传播性癌症DFT2。DFT2引发的面部肿瘤在外观上与DFT1引发的肿瘤无法区分,但在组织学上有所不同。DFT2在细胞遗传学上与DFT1没有可检测到的相似性,并且携带一条Y染色体,这与DFT1的雌性起源形成对比。在微卫星、结构变异和主要组织相容性复合体(MHC)位点上,DFT2与其宿主以及DFT1都显示出不同的等位基因,证实它是另一种能够作为异体、MHC不匹配的移植物在袋獾之间传播的癌症。这些发现表明,袋獾至少产生了两种不同的可传播性癌症谱系,并表明可传播性癌症在自然界中出现的频率可能比之前认为的更高。DFT2的发现给袋獾的保护带来了重大挑战,并增加了这种物种特别容易出现可传播性癌症的可能性。更普遍地说,我们的发现凸显了癌细胞脱离其宿主并成为危险的可传播病原体的可能性。