The Tasmanian Devil Transcriptome Reveals Schwann Cell Origins of a Clonally Transmissible Cancer

Be-Deviled Cancer Recently, a deadly transmissible cancer has emerged in Tasmanian devils, the largest existing marsupial carnivore. This disease, devil facial tumor disease (DFTD), leads to the growth of large facial tumors that frequently metastasize to internal organs. DFTD is thought to be transmitted by biting, and leads to death of affected animals within months, usually by obstructing the animals' ability to feed. Consequently, in the last 10 years Tasmanian devil numbers have dropped by about 60%. There are no genetic tests, vaccines, or treatments available for this disease, and without intervention, models predict that DFTD could cause extinction of Tasmanian devils in the wild within 50 years. Several lines of evidence suggest that DFTD is transmitted as a clonal allograft, whereby the cancer cells themselves are the agents of tumor transmission. Murchison et al. (p. 84) examined this hypothesis in detail by genotyping 25 tumor-host pairs from around Tasmania at 14 microsatellite loci and at a variable mitochondrial polymorphism. DFTD tumors were indeed found to be genetically distinct from their hosts and almost completely genetically identical to one another, supporting the idea of transmission by allograft. Sequencing the Tasmanian devil facial tumor disease provides a potential diagnostic marker. The Tasmanian devil, a marsupial carnivore, is endangered because of the emergence of a transmissible cancer known as devil facial tumor disease (DFTD). This fatal cancer is clonally derived and is an allograft transmitted between devils by biting. We performed a large-scale genetic analysis of DFTD with microsatellite genotyping, a mitochondrial genome analysis, and deep sequencing of the DFTD transcriptome and microRNAs. These studies confirm that DFTD is a monophyletic clonally transmissible tumor and suggest that the disease is of Schwann cell origin. On the basis of these results, we have generated a diagnostic marker for DFTD and identify a suite of genes relevant to DFTD pathology and transmission. We provide a genomic data set for the Tasmanian devil that is applicable to cancer diagnosis, disease evolution, and conservation biology.

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