A genome-wide approach to comparative oncology: high-resolution oligonucleotide aCGH of canine and human osteosarcoma pinpoints shared microaberrations

Abstract

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.