title: A second transmissible cancer in Tasmanian devils.
abstract: 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.
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7000, Australia;
authors.forename: Ruth J
authors.initials: RJ
authors.lastname: Pye
authors.affiliation: Save the Tasmanian Devil Program, Tasmanian Department of Primary Industries, Parks, Water and the Environment, Hobart, TAS 7000, Australia;
authors.forename: David
authors.initials: D
authors.lastname: Pemberton
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7000, Australia;
authors.forename: Cesar
authors.initials: C
authors.lastname: Tovar
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom;
authors.forename: Jose M C
authors.initials: JM
authors.lastname: Tubio
authors.affiliation: Department of Cytogenetics, Royal Hobart Hospital, Hobart, TAS 7000, Australia;
authors.forename: Karen A
authors.initials: KA
authors.lastname: Dun
authors.affiliation: Save the Tasmanian Devil Program, Tasmanian Department of Primary Industries, Parks, Water and the Environment, Hobart, TAS 7000, Australia;
authors.forename: Samantha
authors.initials: S
authors.lastname: Fox
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7000, Australia;
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Darby
authors.affiliation: Mount Pleasant Laboratories, Tasmanian Department of Primary Industries, Parks, Water and the Environment, Prospect, TAS 7250, Australia;
authors.forename: Dane
authors.initials: D
authors.lastname: Hayes
authors.affiliation: Mount Pleasant Laboratories, Tasmanian Department of Primary Industries, Parks, Water and the Environment, Prospect, TAS 7250, Australia;
authors.forename: Graeme W
authors.initials: GW
authors.lastname: Knowles
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7000, Australia;
authors.forename: Alexandre
authors.initials: A
authors.lastname: Kreiss
authors.affiliation: Centre for Biological Science, University of Southampton, Highfield Campus, Southampton SO17 1BJ, United Kingdom;
authors.forename: Hannah V T
authors.initials: HV
authors.lastname: Siddle
authors.affiliation: Mount Pleasant Laboratories, Tasmanian Department of Primary Industries, Parks, Water and the Environment, Prospect, TAS 7250, Australia;
authors.forename: Kate
authors.initials: K
authors.lastname: Swift
authors.affiliation: School of Medicine, University of Tasmania, Hobart, TAS 7000, Australia.
authors.forename: A Bruce
authors.initials: AB
authors.lastname: Lyons
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom; epm27@cam.ac.uk G.M.Woods@utas.edu.au.
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Murchison
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7000, Australia; epm27@cam.ac.uk G.M.Woods@utas.edu.au.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Woods
mesh_terms: D000483:Alleles; D000818:Animals; D019457:Chromosome Breakage; D020732:Cytogenetic Analysis; D005091:Exons / Q000235:genetics; D016678:Genome; D005843:Geography; D006239:Haplotypes / Q000235:genetics; D007621:Karyotyping; D008394:Marsupialia / Q000502:physiology*; D018895:Microsatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013648:Tasmania; D014960:X Chromosome / Q000235:genetics
keywords: Tasmanian devil; Tasmanian devil facial tumor disease; contagious cancer; transmissible cancer