telomere dynamics and homeostasis in a transmissible cancer端粒动力学和体内平衡的传染性癌症.pdf

Telomere Dynamics and Homeostasis in a Transmissible Cancer 1 2 2 2 1 Beata Ujvari , Anne-Maree Pearse , Robyn Taylor , Stephen Pyecroft , Cassandra Flanagan , 1 4,5 3 1 Sara Gombert , Anthony T. Papenfuss , Thomas Madsen , Katherine Belov * 1 Faculty of Veterinary Sciences, University of Sydney, Sydney, Australia, 2 Devil Facial Tumour Project, Diagnostic Services, Animal Health Laboratory, Department of Primary Industries, Water and Environment, Launceston, Tasmania, Australia, 3 School of Biological Sciences, University of Wollongong, Wollongong, Australia, 4 Bioinformatics division, The Walter Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia, 5 Department of Mathematics and Statistics, The University of Melbourne, Melbourne, Victoria, Australia Abstract Background: Devil Facial Tumour Disease (DFTD) is a unique clonal cancer that threatens the world’s largest carnivorous marsupial, the Tasmanian devil (Sarcophilus harrisii) with extinction. This transmissible cancer is passed between individual devils by cell implantation during social interactions. The tumour arose in a Schwann cell of a single devil over 15 years ago and since then has expanded clonally, without showing signs of replicative senescence; in stark contrast to a somatic cell that displays a finite capacity for replication, known as the ‘‘Hayflick limit’’. Methodology/Principal Findings: In the present study we investigate the role of telomere length, measured as Telomere Copy Number (TCN), and telomerase and shelterin gene expression, as well as telomerase activity in maintaining