Abstract
BackgroundUrothelial carcinoma (UC), also known as transitional cell carcinoma (TCC), of the bladder is the most common neoplasm affecting the canine urogenital system. To facilitate study of the disease in vitro, cell line models have been established from primary tumor biopsies. Their resemblance to the primary disease, however, has not been well defined. In the present study, we evaluated five canine UC cell lines via oligonucleotide array comparative genomic hybridization (oaCGH), fluorescence in situ hybridization (FISH), and gene expression analysis.ResultsComparison of genome wide DNA copy number profiles of the cell lines with primary biopsy specimens revealed redundancies in genomic aberrations, indicating that the cell lines retain the gross genomic architecture of primary tumors. As in the primary tumors, gain of canine chromosomes 13 and 36 and loss of chromosome 19 were among the most frequent aberrations evident in the cell lines. FISH analysis revealed chromosome structural aberrations, including tandem duplications, bi-armed chromosomes, and chromosome fusions, suggesting genome instability during neoplastic transformation. Gene expression profiling highlighted numerous differentially expressed genes, including many previously shown as dysregulated in primary canine UC and human bladder cancer. Pathway enrichment analysis emphasized pathways suspected to be at the crux of UC pathogenesis, including xenobiotic and lipid compound metabolism.ConclusionsThese data support valid use of the canine UC cell lines evaluated by confirming they provide an accurate and practical means to interrogate the UC at a molecular level. Moreover, the cell lines may provide a valuable model for furthering our understanding of aberrant metabolic pathways in UC development.Electronic supplementary materialThe online version of this article (doi:10.1186/s40575-015-0028-3) contains supplementary material, which is available to authorized users.
Highlights
Urothelial carcinoma (UC), known as transitional cell carcinoma (TCC), of the bladder is the most common neoplasm affecting the canine urogenital system
We investigated the molecular profile of five canine UC cell lines with oligonucleotide array comparative genomic hybridization and fluorescence in situ hybridization (FISH)
Canine UC cell lines display recurrent chromosome copy number and structural aberrations Metaphase preparations from each of the five canine UC cell lines revealed a high degree of aneuploidy, with an excess of 100 chromosomes in four of five cell lines (Table 1)
Summary
Urothelial carcinoma (UC), known as transitional cell carcinoma (TCC), of the bladder is the most common neoplasm affecting the canine urogenital system. To facilitate study of the disease in vitro, cell line models have been established from primary tumor biopsies. Their resemblance to the primary disease, has not been well defined. Urothelial carcinoma (UC), referred to as transitional cell carcinoma, is the most common bladder neoplasm in the dog [1]. Previous studies have shown that the genomic landscape of canine UC is highly aberrant, with recurrent chromosome copy number aberrations affecting gene dosage on, most notably, canine chromosomes (CFA) 13, 19, and 36 [4]. Previous studies have found that canine UC closely resembles that of the human counterpart, in histopathological features, clinical behavior, and genomic aberrations, furthering the value of the dog to human medicine [2, 6, 4]
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