PMID- 25783786 OWN - NLM STAT- MEDLINE DCOM- 20160203 LR - 20181113 IS - 1573-6849 (Electronic) IS - 0967-3849 (Print) IS - 0967-3849 (Linking) VI - 23 IP - 2 DP - 2015 Jun TI - Canine urothelial carcinoma: genomically aberrant and comparatively relevant. PG - 311-31 LID - 10.1007/s10577-015-9471-y [doi] AB - 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 custom Agilent SureFISH probes, was performed to 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. FAU - Shapiro, S G AU - Shapiro SG AD - Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC, 27607, USA. FAU - Raghunath, S AU - Raghunath S FAU - Williams, C AU - Williams C FAU - Motsinger-Reif, A A AU - Motsinger-Reif AA FAU - Cullen, J M AU - Cullen JM FAU - Liu, T AU - Liu T FAU - Albertson, D AU - Albertson D FAU - Ruvolo, M AU - Ruvolo M FAU - Bergstrom Lucas, A AU - Bergstrom Lucas A FAU - Jin, J AU - Jin J FAU - Knapp, D W AU - Knapp DW FAU - Schiffman, J D AU - Schiffman JD FAU - Breen, M AU - Breen M LA - eng GR - T35 OD011070/OD/NIH HHS/United States GR - T35 RR025837/RR/NCRR NIH HHS/United States GR - T35/PHS HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20150318 PL - Netherlands TA - Chromosome Res JT - Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology JID - 9313452 SB - IM MH - Animals MH - Biopsy MH - Carcinoma/*veterinary MH - *Chromosome Aberrations MH - *Comparative Genomic Hybridization MH - Computational Biology/methods MH - DNA Copy Number Variations MH - Dogs MH - Female MH - Genetic Loci MH - Genomics/methods MH - Humans MH - In Situ Hybridization, Fluorescence MH - Male MH - Urologic Neoplasms/*veterinary PMC - PMC4501039 MID - NIHMS702432 EDAT- 2015/03/19 06:00 MHDA- 2016/02/04 06:00 PMCR- 2015/07/14 CRDT- 2015/03/19 06:00 PHST- 2015/01/10 00:00 [received] PHST- 2015/02/10 00:00 [accepted] PHST- 2015/02/07 00:00 [revised] PHST- 2015/03/19 06:00 [entrez] PHST- 2015/03/19 06:00 [pubmed] PHST- 2016/02/04 06:00 [medline] PHST- 2015/07/14 00:00 [pmc-release] AID - 10.1007/s10577-015-9471-y [doi] PST - ppublish SO - Chromosome Res. 2015 Jun;23(2):311-31. doi: 10.1007/s10577-015-9471-y. Epub 2015 Mar 18.