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Article

Development of a Genome-Wide Oligonucleotide Microarray Platform for Detection of DNA Copy Number Aberrations in Feline Cancers

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Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA
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Comparative Medicine Institute, North Carolina State University, Raleigh, NC 27606, USA
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Laboratory of Genomic Diversity, Basic Research Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute-Frederick, Frederick, MD 21702, USA
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Present address: JP Solutions, Ellicott City MD 21042, USA
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Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA
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Center for Human Health and the Environment, North Carolina State University, Raleigh, NC 27607, USA
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Cancer Genetics Program, UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC 27514, USA
*
Author to whom correspondence should be addressed.
Vet. Sci. 2020, 7(3), 88; https://doi.org/10.3390/vetsci7030088
Received: 14 May 2020 / Revised: 25 June 2020 / Accepted: 30 June 2020 / Published: 7 July 2020
The utility of the domestic cat as a model system for biomedical studies was constrained for many years by the absence of a comprehensive feline reference genome sequence assembly. While such a resource now exists, the cat continues to lag behind the domestic dog in terms of integration into the ‘One Health’ era of molecular medicine. Stimulated by the advances being made within the evolving field of comparative cancer genomics, we developed a microarray platform that allows rapid and sensitive detection of DNA copy number aberrations in feline tumors using comparative genomic hybridization analysis. The microarray comprises 110,456 unique oligonucleotide probes anchored at mean intervals of 22.6 kb throughout the feline reference genome sequence assembly, providing ~350-fold higher resolution than was previously possible using this technique. We demonstrate the utility of this resource through genomic profiling of a feline injection-site sarcoma case, revealing a highly disrupted profile of DNA copy number imbalance involving several key cancer-associated genes including KIT, TP53, PTEN, FAS and RB1. These findings were supported by targeted fluorescence in-situ hybridization analysis, which identified major alterations in chromosome structure, including complex intrachromosomal reorganization events typical of those seen in aggressive soft-tissue sarcomas of other species. We then characterized a second mass that was identified at a nearby site in the same patient almost 12 months later. This mass demonstrated a remarkably conserved genomic profile consistent with a recurrence of the original tumor; however the detection of subtle differences reflected evolution of the tumor over time. These findings exemplify the diverse potential of this microarray platform to incorporate domestic cat cancers into comparative and translational research efforts in molecular oncology. View Full-Text
Keywords: feline; cat; cancer; genomics; chromosome; comparative genomic hybridization (CGH) feline; cat; cancer; genomics; chromosome; comparative genomic hybridization (CGH)
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MDPI and ACS Style

Thomas, R.; Pontius, J.U.; Borst, L.B.; Breen, M. Development of a Genome-Wide Oligonucleotide Microarray Platform for Detection of DNA Copy Number Aberrations in Feline Cancers. Vet. Sci. 2020, 7, 88. https://doi.org/10.3390/vetsci7030088

AMA Style

Thomas R, Pontius JU, Borst LB, Breen M. Development of a Genome-Wide Oligonucleotide Microarray Platform for Detection of DNA Copy Number Aberrations in Feline Cancers. Veterinary Sciences. 2020; 7(3):88. https://doi.org/10.3390/vetsci7030088

Chicago/Turabian Style

Thomas, Rachael, Joan U Pontius, Luke B Borst, and Matthew Breen. 2020. "Development of a Genome-Wide Oligonucleotide Microarray Platform for Detection of DNA Copy Number Aberrations in Feline Cancers" Veterinary Sciences 7, no. 3: 88. https://doi.org/10.3390/vetsci7030088

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