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

Veterinary Sciences

Rachael Thomas¹  Matthew Breen¹  LukeB Borst²  JoanU Pontius³ 

[1] Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA;Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA;Laboratory of Genomic Diversity, Basic Research Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute-Frederick, Frederick, MD 21702, USA;

关键词: feline;    cat;    cancer;    genomics;    chromosome;    comparative genomic hybridization (CGH);   

DOI  :  10.3390/vetsci7030088

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown