Evolution of a contagious cancer: epigenetic variation in Devil Facial Tumour Disease
- Ujvari, B; Pearse, AM; Peck, S; Harmsen, C; Taylor, R; Pyecroft, S; Madsen, T; Papenfuss, AT; Belov, K;
Publication Year 2013-01-07, Volume 280, Issue #1750, Page -
- Journal Title
- PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
- Publication Type
- Journal Article
- 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.
- ROYAL SOC
- cancer ; DNA methylation ; epigenetic ; evolution ; Tasmanian devil (Sarcophilus harrisii) ;marsupial
- WEHI Research Division(s)
- Link To PubMed Central Version
- Publisher's Version
- Rights Notice
- © 2012 The Author(s) Published by the Royal Society. All rights reserved.
Creation Date: 2013-01-07 12:00:00Last Modified: 0001-01-01 12:00:00