caa a22 4500 606190767 CHVBK 20210128100856.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s10577-015-9471-y doi (NATIONALLICENCE)springer-10.1007/s10577-015-9471-y Canine urothelial carcinoma: genomically aberrant and comparatively relevant [Elektronische Daten] [S. Shapiro, S. Raghunath, C. Williams, A. Motsinger-Reif, J. Cullen, T. Liu, D. Albertson, M. Ruvolo, A. Bergstrom Lucas, J. Jin, D. Knapp, J. Schiffman, M. Breen] Urothelial carcinoma (UC), also referred to as transitional cell carcinoma (TCC), is the most common bladder malignancy in both human and canine populations. In human UC, numerous studies have demonstrated the prevalence of chromosomal imbalances. Although the histopathology of the disease is similar in both species, studies evaluating the genomic profile of canine UC are lacking, limiting the discovery of key comparative molecular markers associated with driving UC pathogenesis. In the present study, we evaluated 31 primary canine UC biopsies by oligonucleotide array comparative genomic hybridization (oaCGH). Results highlighted the presence of three highly recurrent numerical aberrations: gain of dog chromosome (CFA) 13 and 36 and loss of CFA 19. Regional gains of CFA 13 and 36 were present in 97 %and 84% of cases, respectively, and losses on CFA 19 were present in 77% of cases. Fluorescence in situ hybridization (FISH), using targeted bacterial artificial chromosome (BAC) clones and customAgilent SureFISH probes, was performedto detect and quantify these regions in paraffin-embedded biopsy sections and urine-derived urothelial cells. The data indicate that these three aberrations are potentially diagnostic of UC. Comparison of our canine oaCGH data with that of 285 human cases identified a series of shared copy number aberrations. Using an informatics approach to interrogate the frequency of copy number aberrations across both species, we identified those that had the highest joint probability of association with UC. The most significant joint region contained the gene PABPC1, which should be considered further for its role in UC progression. In addition, cross-species filtering of genome-wide copy number data highlighted several genes as high-profile candidates for further analysis, including CDKN2A, S100A8/9, and LRP1B. We propose that these common aberrations are indicative of an evolutionarily conserved mechanism of pathogenesis and harbor genes key to urothelial neoplasia, warranting investigation for diagnostic, prognostic, and therapeutic applications. Springer Science+Business Media Dordrecht, 2015 Canine nationallicence Urothelial carcinoma nationallicence Transitional cell carcinoma nationallicence Cytogenetics nationallicence Chromosome aberration nationallicence Array comparative genomic hybridization nationallicence Comparative oncology nationallicence AMADID : Agilent MicroArray Design Identifier nationallicence BAC : Bacterial artificial chromosome nationallicence CDKN2A : Cyclin-dependent kinase inhibitor 2A nationallicence CFA : Canis familiaris (also used as a prefix to caninechromosome numbers) nationallicence CNA : Copy number aberration nationallicence DNA : Deoxyribonucleic acid nationallicence ECCS : Evolutionarily conserved chromosome segment nationallicence FASST2 : Fast Adaptive States Segmentation Technique 2 nationallicence FFPE : Formalin-fixed paraffin embedded nationallicence FISH : Fluorescence in situ hybridization nationallicence GO : Gene ontology nationallicence H&E : Hematoxylin and eosin nationallicence HSA : Homo sapiens (also used as a prefix to humanchromosome numbers) nationallicence oaCGH : Oligo-array comparative genomic hybridization nationallicence OR : Odds ratio nationallicence PANTHER : Protein Analysis Through Evolutionary Relationships nationallicence PBS : Phosphate-buffered saline nationallicence RR : Relative risk nationallicence UC : Urothelial carcinoma nationallicence TCC : Transitional cell carcinoma nationallicence Shapiro S. Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, 27607, Raleigh, NC, USA aut Raghunath S. Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, 27607, Raleigh, NC, USA aut Williams C. Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, 27607, Raleigh, NC, USA aut Motsinger-Reif A. Department of Statistics, College of Sciences, North Carolina State University, Raleigh, NC, USA aut Cullen J. Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA aut Liu T. Anatomic Pathology Division Department of Pathology, University of Utah, 1950 Circle of Hope, RM N3105, 84112, Salt Lake City, UT, USA aut Albertson D. Anatomic Pathology Division Department of Pathology, University of Utah, 1950 Circle of Hope, RM N3105, 84112, Salt Lake City, UT, USA aut Ruvolo M. Agilent Technologies, 5301 Stevens Creek Blvd., 95051, Santa Clara, CA, USA aut Bergstrom Lucas A. Agilent Technologies, 5301 Stevens Creek Blvd., 95051, Santa Clara, CA, USA aut Jin J. Agilent Technologies, 5301 Stevens Creek Blvd., 95051, Santa Clara, CA, USA aut Knapp D. Department of Veterinary Clinical Sciences, Purdue University, School of Veterinary Medicine, West Lafayette, IN, USA aut Schiffman J. Department of Pediatrics and Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, 84112, Salt Lake City, UT, USA aut Breen M. Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, 27607, Raleigh, NC, USA aut Chromosome Research Springer Netherlands 23/2(2015-06-01), 311-331 0967-3849 23:2<311 2015 23 10577 https://doi.org/10.1007/s10577-015-9471-y text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10577-015-9471-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Shapiro S. Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, 27607, Raleigh, NC, USA aut NATIONALLICENCE 700 1- Raghunath S. Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, 27607, Raleigh, NC, USA aut NATIONALLICENCE 700 1- Williams C. Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, 27607, Raleigh, NC, USA aut NATIONALLICENCE 700 1- Motsinger-Reif A. Department of Statistics, College of Sciences, North Carolina State University, Raleigh, NC, USA aut NATIONALLICENCE 700 1- Cullen J. Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA aut NATIONALLICENCE 700 1- Liu T. Anatomic Pathology Division Department of Pathology, University of Utah, 1950 Circle of Hope, RM N3105, 84112, Salt Lake City, UT, USA aut NATIONALLICENCE 700 1- Albertson D. Anatomic Pathology Division Department of Pathology, University of Utah, 1950 Circle of Hope, RM N3105, 84112, Salt Lake City, UT, USA aut NATIONALLICENCE 700 1- Ruvolo M. Agilent Technologies, 5301 Stevens Creek Blvd., 95051, Santa Clara, CA, USA aut NATIONALLICENCE 700 1- Bergstrom Lucas A. Agilent Technologies, 5301 Stevens Creek Blvd., 95051, Santa Clara, CA, USA aut NATIONALLICENCE 700 1- Jin J. Agilent Technologies, 5301 Stevens Creek Blvd., 95051, Santa Clara, CA, USA aut NATIONALLICENCE 700 1- Knapp D. Department of Veterinary Clinical Sciences, Purdue University, School of Veterinary Medicine, West Lafayette, IN, USA aut NATIONALLICENCE 700 1- Schiffman J. Department of Pediatrics and Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, 84112, Salt Lake City, UT, USA aut NATIONALLICENCE 700 1- Breen M. Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, 27607, Raleigh, NC, USA aut NATIONALLICENCE 773 0- Chromosome Research Springer Netherlands 23/2(2015-06-01), 311-331 0967-3849 23:2<311 2015 23 10577