GENE-14. COMPARATIVE CYTOGENETIC ANALYSIS OF DOG AND HUMAN CHOROID PLEXUS TUMORS DEFINES SYNTENIC REGIONS OF GENOMIC LOSS

Spontaneously occurring choroid plexus tumors (CPTs) in dogs are indistinguishable from human tumor counterparts based on histology and imaging. Leveraging karyotypic differences between dogs and humans may provide insight into evolutionarily conserved cytogenetic alterations and allow for more focussed analysis of orthologous regions within large human chromosomal losses and gains. We used Illumina 173K HD SNP arrays to determine copy number alterations (CNAs) in 12 histologically confirmed spontaneous canine choroid plexus tumor samples (3 papillomas/CPP, 8 carcinomas/CPC, 1 recurrent CPP) and tumor matched normal tissue. Copy number calls and allelic events were determined by matched paired analysis using BioDiscovery Nexus Copy Number^TM software. Hierarchical clustering by aberration profile did not distinguish between CPPs and CPCs. Choroid plexus tumors were characterized by highly recurrent single copy, whole chromosomal losses. Loss of chromosomes CFA 2, and 20 occurred in 100% tumors and losses of CFA 5 and 8 were seen in >90% of tumors. Genes associated with chromosomal instability in these regions included TP53, VHL, CENPH, AURKB, HAUS8 and KIF2A. Using the TSGene2.0 database we identified loss of 53, 61, 75 and 21 candidate tumor suppressor genes on chromosomes 2, 20, 5 and 8 respectively. The pattern of predominantly whole chromosomal losses was most similar to findings in human CPCs compared to CPPs and aCPPs. Several recurrent whole chromosomal losses in dog tumors contained deletions orthologous to regions of some of the most frequently reported whole chromosomal losses in human CPTs, including regions of HSA 3, 11, 16 and 17. The striking prevalence of specific CNAs in dog CPTs is supportive of their biological relevance in CPT oncogenesis and progression. Further analysis of gene expression and concordance with orthologous CNAs may further focus efforts to define common key genetic alterations in the genesis and progression of these tumors across the two species.