Project description:The canine transmissible veneral tumour (CTVT) is one of the few known clonally transmissible cancers in nature. CTVT regresses spontaneously or after a single treatment with vincristine, however we know little of the mechanisms. To understand CTVT regression, we performed methylome analyses on serial biopsies of regressing and non-regressing CTVT, aiming to identify the likely drivers of CTVT regression.
Project description:To assess expression of mtDNA genes in the canine transmissible venereal tumour (CTVT), biopsy tissue samples from 33 CTVT cases were subjected to total RNA extraction, and stranded RNA sequencing libraries generated with the Ribo-Zero ribosomal RNA removal kit (insert size 100–300 bp) were sequenced using 75-bp paired-end sequencing reads on an Illumina HiSeq4000 instrument. Gene transcript abundance was quantified using the Salmon software (v0.8.2).
Project description:The canine transmissible veneral tumour (CTVT) is one of the few known clonally transmissible cancers in nature. CTVT regresses spontaneously or after a single treatment with vincristine, however we know little of the mechanisms. To understand CTVT regression, we performed transcriptional analyses on serial biopsies of regressing and non-regressing CTVT, aiming to identify the likely drivers of CTVT regression.
Project description:The canine transmissible veneral tumour (CTVT) is one of the few known clonally transmissible cancers in nature. CTVT regresses spontaneously or after a single treatment with vincristine, however we know little of the mechanisms. To understand CTVT regression, we performed transcriptional analyses on serial biopsies of regressing and non-regressing CTVT, aiming to identify the likely drivers of CTVT regression.
Project description:Mammary cancer is the most common type of cancer in female dogs with a lifetime risk of over 24% when dogs are not spayed. The elucidation of the complete canine genome opens new areas for development of cancer therapies. These should be tested first by in vitro models such as cell lines. However, to date, no canine mammary cell lines have been characterized by expression profiling. In this study, canine mammary tumour cell lines with histologically distinct primary tumours of origin were characterized using a newly developed canine cDNA microarray. Comparisons of gene expression profiles showed enrichment for distinct biological pathways and were related to biological properties of the cell lines such as growth rate and in vitro tumourigenicity. Additionally, gene expression profiles of cell lines also showed correspondence to their tumour of origin. Major differences were found in Wnt, cell cycle, cytokine/Rho-GTPase, alternative complement and integrin signalling pathways. Because these pathways show an overlap at the molecular level with those found in human breast cancer, the expression profiling of spontaneous canine mammary cancer may also function as a biological sieve to identify conserved gene expression or pathway profiles of evolutionary significance that are involved in tumourigenesis. These results are the basis for further characterization of canine mammary carcinomas and development of new therapies directed towards specific pathways. In addition these cell lines can be used to further investigate identified deregulated pathways and characterize until now unannotated genes. Keywords: cell line type comparision
Project description:Canine mast cell tumour proliferation depends to a large extent on the activity of KIT, a tyrosine kinase receptor. Inhibitors of the KIT tyrosine kinase have recently been introduced and successfully applied as a therapeutic agent for this tumour type. However, little is known on the downstream target genes of this signalling pathway and molecular changes after inhibition. Transcriptome analysis of the canine mast cell tumour cell line C2 treated for up to 72 hours with the tyrosine kinase inhibitor masitinib identified significant changes in the expression levels of approximately 3500 genes representing 16% of the canine genome. Approximately 40% of these genes had increased mRNA expression levels including genes associated with the pro-proliferative pathways of B- and T-cell receptors, chemokine receptors, steroid hormone receptors and EPO-, RAS and MAP kinase signalling. Proteome analysis of C2 cells treated for 72 hours identified 24 proteins with changed expression levels, most of which being involved in gene transcription, e.g. EIA3, EIA4, TARDBP, protein folding, e.g. HSP90, UCHL3, PDIA3 and protection from oxidative stress, GSTT3, SELENBP1. Transcriptome and proteome analysis of neoplastic canine mast cells treated with masitinib confirmed the strong important and complex role of KIT in these cells. Approximately 16% of the total canine genome and thus the majority of the active genes were significantly transcriptionally regulated. Most of these changes were associated with reduced proliferation and metabolism of treated cells. Interestingly, several pro-proliferative pathways were up-regulated which may represent attempts of masitinib treated cells to activate alternative pro-proliferative pathways. These pathways may contain hypothetical targets for a combination therapy with masitinib to further improve its therapeutic effect. The present study aimed at identifying the transcriptional and translational responses of neoplastic canine mast cells to the tyrosine kinase inhibitor masitinib. To this end, C2 cells, a cell line with a tandem duplication in the juxtamembrane unit and thus constitutively activated KIT, were treated with masitinib and changes in the global mRNA and protein expression levels were characterized.