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
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.
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:Tasmanian devils are threatened with extinction because of two genetically independent transmissible cancers which are termed as Devil Facial Tumour Disease one and two (DFTD-1 and DFTD-2). The cancers are indistinguishable by gross examination and require laboratory procedures such as immunohistochemistry and/or PCR for diagnosis. Here we used proteomics to analyse extracellular vesicles from DFTD cells to better understand the potentail role of EV's in DFTD cancer metastasis.
2023-04-27 | PXD020766 | Pride
Project description:A transmissible cancer shifts from emergence to endemism in Tasmanian devils
Project description:The marsupial Tasmanian devil (Sarcophilus harrisii) faces extinction due to transmissible devil facial tumor disease (DFTD). To unveil the culprit molecular underpinnings, we designed an approach that combines sensitivity to drugs with an integrated systems-biology characterization. Sensitivity to inhibitors of the ERBB family of receptor tyrosine kinases correlated with their overexpression, suggesting a causative link. Proteomic and DNA methylation analyses revealed tumor-specific signatures linked to oncogenic signaling hubs including evolutionary conserved STAT3. Indeed, inhibition of ERBB blocked phosphorylation of STAT3 and arrested cancer cells. Blockade of ERBB signaling prevented tumor growth in a xenograft model and resulted in recovery of MHC-I gene expression. This link between the hyperactive ERBB-STAT3 axis and decreased MHC-I mediated tumor immunosurveillance provides mechanistic insights into horizontal transmissibility and lets us propose a dual chemo-immunotherapeutic strategy to save Tasmanian devils from DFTD.
Project description:Serum extracellular vesicles were obtained from Tasmanian devils with confirmed DFTD, heathy devils from captive and wild populations and from latent devils with no evidence of facial tumours.
Project description:Transmissible cancers are spread via the passage of malignant cells. The survival of the Tasmanian devil, the largest marsupial carnivore, is threatened by two independent transmissible cancers, devil facial tumour (DFT) 1 and devil facial tumour 2 (DFT2). To aid the development of a peptide vaccine and to interrogate how histocompatibility barriers can be overcome, we analysed the peptides bound to Major Histocompatibility Complex class I molecules from the Tasmanian devil and its transmissible tumours.
