ujvari-evolution-2012.pdf (517.82 kB)
Evolution of a contagious cancer: epigenetic variation in devil facial tumour disease
journal contribution
posted on 2012-01-01, 00:00 authored by Beata UjvariBeata Ujvari, A M Pearse, S Peck, C Harmsen, R Taylor, S Pyecroft, Thomas MadsenThomas Madsen, A Papenfuss, K BelovThe 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.
History
Journal
Proceedings of the Royal Society B: biological sciencesVolume
280Issue
1750Pagination
2 - 8Publisher
Royal Society PublishingLocation
London, Eng.Publisher DOI
Link to full text
ISSN
1471-2954Language
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2012, Royal Society PublishingUsage metrics
Categories
No categories selectedKeywords
cancerDNA methylationepigeneticevolutiontasmanian devilsarcophilius harrisiimarsupialScience & TechnologyLife Sciences & BiomedicineBiologyEcologyEvolutionary BiologyLife Sciences & Biomedicine - Other TopicsEnvironmental Sciences & EcologyTasmanian devil (Sarcophilus harrisii)COPY-NUMBER-VARIATIONSARCOPHILUS-HARRISIITRANSMISSIBLE CANCERPOPULATION-STRUCTUREGENETIC DIVERSITYDEMETHYLATIONEXPRESSIONMETHYLTRANSFERASES
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC