Molecular cytogenetic evaluation of human osteosarcoma (OS) has revealed the characteristically high degree of genomic reorganization that is the hallmark of this cancer. The extent of genomic disorder in OS has hindered identification of the genomic aberrations driving disease progression. With pathophysiological similarities to its human counterpart, canine OS represents an ideal model for comparison of conserved regions of genomic instability that may be disease-associated rather than genomic passengers. This study used high-resolution oligonucleotide array comparative genomic hybridization and a variety of informatics tools to aid in the identification of disease-associated genome-wide DNA copy number aberrations in canine and human OS. Our findings support and build upon the high level of cytogenetic complexity, through the identification of shared regions of microaberration (<500 kb) and functional analysis of possible orthologous OS-associated genes to pinpoint the cellular processes most commonly affected by aberration in human and canine OS. Aberrant regions contained previously reported genes such as CDC5L, MYC, RUNX2, and CDKN2A/. CDKN2B, while expanding the gene of interest list to include ADAM15, CTC1, MEN1, CDK7, and others. Such regions of instability may thus have functional significance in the etiology of OS, the most common primary bone tumor in both species.
Bibliographical noteFunding Information:
This work was supported in part by funds from the American Kennel Club Canine Health Foundation (Grants 947A and 947B ) awarded to M.B. and J.M. A.A. was a recipient of an NCSU Functional Genomics Graduate Fellowship. We thank Dr. Rachael Thomas for useful discussion regarding oligo-aCGH analysis. We also acknowledge the grant funding from the Academic Health Center , Masonic Cancer Center , University of Minnesota and Karen Wyckoff Rein in the Sarcoma (KWRIS) Foundation (Based in MN) for funding to S.S. and J.F.M. Funds provided by the Kate Koogler Canine Cancer Fund and the Animal Cancer Care and Research Program of the University of Minnesota helped defray recruitment costs for dogs with OS. We thank Susan Fosmire, Milcah Scott, and Mitzi Lewellen for technical assistance and for maintaining the canine sample biorepository.
Copyright 2013 Elsevier B.V., All rights reserved.
- Comparative oncology