Development of a Genome-Wide Oligonucleotide Microarray Platform for Detection of DNA Copy Number Aberrations in Feline Cancers
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 ‘On...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Veterinary Sciences |
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| Online Access: | https://www.mdpi.com/2306-7381/7/3/88 |
| _version_ | 1797563184331096064 |
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| author | Rachael Thomas Joan U Pontius Luke B Borst Matthew Breen |
| author_facet | Rachael Thomas Joan U Pontius Luke B Borst Matthew Breen |
| author_sort | Rachael Thomas |
| collection | DOAJ |
| description | 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 <i>KIT,</i> <i>TP53</i>, <i>PTEN, FAS</i> and <i>RB1</i>. 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. |
| first_indexed | 2024-03-10T18:38:56Z |
| format | Article |
| id | doaj.art-d8853aa816534d97b046d523f7e45ea3 |
| institution | Directory Open Access Journal |
| issn | 2306-7381 |
| language | English |
| last_indexed | 2024-03-10T18:38:56Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Veterinary Sciences |
| spelling | doaj.art-d8853aa816534d97b046d523f7e45ea32023-11-20T06:03:16ZengMDPI AGVeterinary Sciences2306-73812020-07-01738810.3390/vetsci7030088Development of a Genome-Wide Oligonucleotide Microarray Platform for Detection of DNA Copy Number Aberrations in Feline CancersRachael Thomas0Joan U Pontius1Luke B Borst2Matthew Breen3Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USALaboratory of Genomic Diversity, Basic Research Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute-Frederick, Frederick, MD 21702, USADepartment of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USADepartment of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USAThe 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 <i>KIT,</i> <i>TP53</i>, <i>PTEN, FAS</i> and <i>RB1</i>. 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.https://www.mdpi.com/2306-7381/7/3/88felinecatcancergenomicschromosomecomparative genomic hybridization (CGH) |
| spellingShingle | Rachael Thomas Joan U Pontius Luke B Borst Matthew Breen Development of a Genome-Wide Oligonucleotide Microarray Platform for Detection of DNA Copy Number Aberrations in Feline Cancers Veterinary Sciences feline cat cancer genomics chromosome comparative genomic hybridization (CGH) |
| title | Development of a Genome-Wide Oligonucleotide Microarray Platform for Detection of DNA Copy Number Aberrations in Feline Cancers |
| title_full | Development of a Genome-Wide Oligonucleotide Microarray Platform for Detection of DNA Copy Number Aberrations in Feline Cancers |
| title_fullStr | Development of a Genome-Wide Oligonucleotide Microarray Platform for Detection of DNA Copy Number Aberrations in Feline Cancers |
| title_full_unstemmed | Development of a Genome-Wide Oligonucleotide Microarray Platform for Detection of DNA Copy Number Aberrations in Feline Cancers |
| title_short | Development of a Genome-Wide Oligonucleotide Microarray Platform for Detection of DNA Copy Number Aberrations in Feline Cancers |
| title_sort | development of a genome wide oligonucleotide microarray platform for detection of dna copy number aberrations in feline cancers |
| topic | feline cat cancer genomics chromosome comparative genomic hybridization (CGH) |
| url | https://www.mdpi.com/2306-7381/7/3/88 |
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