title: Evolution of a contagious cancer: epigenetic variation in Devil Facial Tumour Disease.
abstract: The emergence of Devil Facial Tumour Disease (DFTD), a highly contagious cancer, is driving Tasmanian devils (Sarcophilus harrisii) to extinction. The cancer is a genetically and chromosomally stable clonal cell line which is transmitted by biting during social interactions. In the present study, we explore the Devil Facial Tumour (DFT) epigenome and the genes involved in DNA methylation homeostasis. We show that tumour cells have similar levels of methylation to peripheral nerves, the tissue from which DFTD originated. We did not observe any strain or region-specific epimutations. However, we revealed a significant increase in hypomethylation in DFT samples over time (p < 0.0001). We propose that loss of methylation is not because of a maintenance deficiency, as an upregulation of DNA methyltransferase 1 gene was observed in tumours compared with nerves (p < 0.005). Instead, we believe that loss of methylation is owing to active demethylation, supported by the temporal increase in MBD2 and MBD4 (p < 0.001). The implications of these changes on disease phenotypes need to be explored. Our work shows that DFTD should not be treated as a static entity, but rather as an evolving parasite with epigenetic plasticity. Understanding the role of epimutations in the evolution of this parasitic cancer will provide unique insights into the role of epigenetic plasticity in cancer evolution and progression in traditional cancers that arise and die with their hosts.
authors.affiliation: Faculty of Veterinary Sciences, University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Beata
authors.initials: B
authors.lastname: Ujvari
authors.forename: Anne-Maree
authors.initials: AM
authors.lastname: Pearse
authors.forename: Sarah
authors.initials: S
authors.lastname: Peck
authors.forename: Collette
authors.initials: C
authors.lastname: Harmsen
authors.forename: Robyn
authors.initials: R
authors.lastname: Taylor
authors.forename: Stephen
authors.initials: S
authors.lastname: Pyecroft
authors.forename: Thomas
authors.initials: T
authors.lastname: Madsen
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Papenfuss
authors.forename: Katherine
authors.initials: K
authors.lastname: Belov
mesh_terms: D054458:Amplified Fragment Length Polymorphism Analysis / Q000662:veterinary; D000818:Animals; D060965:Clonal Evolution; D019175:DNA Methylation; D056727:Endangered Species; D044127:Epigenesis, Genetic; D005145:Face / Q000473:pathology; D005153:Facial Neoplasms / Q000235:genetics / Q000378:metabolism / Q000662:veterinary*; D015972:Gene Expression Regulation, Neoplastic; D006706:Homeostasis; D008394:Marsupialia / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D010525:Peripheral Nerves / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D013648:Tasmania