Project description:Devil facial tumour disease 1 and 2 (DFT1 and DFT2) are two genetically distinct transmissible cancers endangering the survival of the Tasmanian devil (Sarcophilus harrisii). DFT1 first arose from a cell of the Schwann cell lineage, however, the tissue-of-origin of the recently discovered DFT2 cancer remains unknown. Here we have performed mRNA and protein expression analyses to show that variation in expression patterns between DFT1 and DFT2 tumours is low. Furthermore, DFT2 cells express a range of markers associated with Schwann cell differentiation, suggesting a similar tissue-of-origin to DFT1 tumours. These findings suggest that devils may be predisposed to transmissible cancers of Schwann cell origin. The emergence of these two unique cancers presents an unprecedented opportunity to gain insight into cancer development in animal species.
Project description:The iconic Tasmanian devil (Sarcophilus harrisii) is endangered due to the transmissible cancer Devil Facial Tumour Disease (DFTD), of which there are two genetically independent subtypes (DFT1 and DFT2). While DFT1 and DFT2 can be differentially diagnosed using tumour biopsies, there is an urgent need to develop less invasive biomarkers that can detect DFTD and distinguish between subtypes. Extracellular vesicles (EVs), the nano-sized membrane-enclosed vesicles present in most biofluids, represent a valuable resource for biomarker discovery. Here, we characterized the proteome of EVs from cultured DFTD cells using data independent acquisition mass spectrometry and an in-house spectral library of >1,500 proteins. EVs from both DFT1 and DFT2 cell lines expressed higher levels of proteins associated with focal adhesion functions. Furthermore, hallmark proteins of epithelial mesenchymal transition were enriched in DFT2 EVs relative to DFT1 EVs. These findings were validated in clinical samples, revealing that the mesenchymal marker tenascin-C was also enriched in EVs derived from the serum of devils infected with DFT2 relative to those infected with DFT1 and healthy controls. This first EV-based investigation of DFTD increases our understanding of the cancers’ EVs and their possible involvement in DFTD progression, such as metastasis. Finally, we demonstrated the potential of EVs to differentiate between DFT1 and DFT2 that highlights their potential use as less invasive liquid biopsies for the Tasmanian devil and other animals.
Project description:The Tasmanian devil, a marsupial carnivore, is endangered due to the emergence of a clonally 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, mitochondrial genome analysis, as well as deep sequencing of the DFTD transcriptome and miRNAs. 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 of relevance to DFTD pathology and transmission. We provide a genomic dataset for the Tasmanian devil, which is applicable to cancer diagnosis, disease evolution and conservation biology. This submission contains only small RNA sequence data from this study. Small RNA (18 - 24 nt) sequences from 15 Tasmanian devil (Sarcophilus harrisii) tissue samples
