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:Purpose: To asses the transcriptome of 4 strains of the Tasmanian Devil facial tumor and one healthy fibroblast cell line. Methods: DFTD cells were grown from primary cell cultures derived from fine needle aspirates that have been collected from the wild. Total RNA from devil facial tumor strains 1-4 and the fibroblast was isolated from approximately 1 x 10^6 cells using QIAzol lysis reagent according to the manufacturer’s instructions (Qiagen). RNA-seq libraries were prepared with TruSeq Stranded mRNA LT sample preparation kit (Illumina) using Sciclone and Zephyr liquid handling robotics (PerkinElmer). The 5 libraries were pooled, diluted and sequenced on Illumina HiSeq 3000/4000 using 75 bp paired-end chemistry. Base calls provided by the Illumina Realtime Analysis software were converted into BAM format using Illumina2bam and demultiplexed using BamIndexDecoder. Paired-end reads were trimmed for adaptor sequences and filtered with the trimmomatic tool. Trimmed reads were aligned on the version 7.0 of the Tasmanian Devil with the STAR aligner. Counting of reads on annotated transcripts (Sarcophilus_harrisii.DEVIL7.0.90.gtf from Ensembl) was performed with featurecounts on fragments. The DESeq2 Biconductor library has been used for counts normalization and differential analysis between the transcriptomes of the four DFTD and fibroblast cell lines
Project description:The Tasmanian devil is the only mammalian species harbouring two lineages of contagious cancer within its population. This dataset represents the proteomics analysis of DFT1, DFT2 and SALEM lines.
Project description:Purpose: Depict the landscape of epigenetic regulation in Tasmanian devil facial tumor biopsies. Differential analysis of healthy versus tumor biopsies highlighted 166 candidate genes with different DNA methylation levels in their promoters, which included the tumor-specific hypermethylated promoters of Estrogen Receptor 1 (ESR1) and the transcription factor GATA3.
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: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.
