Abstract
Mast cell tumours (MCTs) are the most common skin tumours in dogs. Their clinical behaviour is variable and their aetiology remains largely unknown. We performed a metaphase fluorescence in situ hybridisation (FISH) with whole chromosome painting probes, and interphase FISH with BAC probes for 14 cancer-related genes to reveal clonal structural chromosome rearrangements and copy number variants (CNVs) in canine cutaneous MCTs. The metaphase FISH performed in three MCTs revealed several clonal monosomies and trisomies and two different chromosome rearrangements. No centric fusions were detected. The interphase FISH showed a variety of low frequency CNVs for the individual cancer-related genes. The heterogeneous character of the detected abnormalities indicates increased chromosome instability in canine MCTs. The clonal gain of chromosome 11 was detected in 81% (13/16) of the MCTs. Further research is needed to evaluate the significance of this abnormality as prognostic factor for the survival time or recurrence risk assessments in canine cutaneous MCTs.
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Acknowledgements
The authors are grateful to the dog owners and to veterinarians J. Pfeifr, J. Bezdek and T. Fiala who collected the blood and tumour samples at the Veterinary Clinic Animed, Brno, at the Small Animal Clinic, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences Brno, and at Veterinary Hospital AA-Vet, Prague, Czech Republic.
Funding
This work was supported by the grant 16-26655S from the Czech Science Foundation (GA CR), by the Ministry of Agriculture (RO 0518) and by the Ministry of Education, Youth and Sports of the Czech Republic under the project CEITEC 2020 (LQ1601).
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The study complies with the current laws of the Czech Republic. All applicable international, national and institutional guidelines for the care and use of animals were followed. This article does not contain any studies using human subjects.
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Communicated by: Maciej Szydlowski
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Supplemental Table S1
Combinations of the red fox whole chromosome painting probes used for the screening of canine MCTs and their orthology with canine chromosomes (according to Becker et al. 2011). The vulpine probes were labelled with Spectrum Green (SG), Spectrum Orange (SO), Biotin (Bio) and Digoxigenin (Dig). (DOC 43 kb)
Supplemental Table S2
BAC probes used for the interphase FISH analysis of cancer-related genes and their localisation on canine chromosomes. (DOC 34 kb)
Supplemental Figure 1
Complex rearrangement t(X;4;5) analysed by FISH using BAC probes for TP53 and FAT2 genes (a) and the locus-specific probe for the PDGFRB gene (b). (DOC 510 kb)
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Vozdova, M., Kubickova, S., Cernohorska, H. et al. Structural and copy number chromosome abnormalities in canine cutaneous mast cell tumours. J Appl Genetics 60, 63–70 (2019). https://doi.org/10.1007/s13353-018-0471-4
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DOI: https://doi.org/10.1007/s13353-018-0471-4