COMPARATIVE CYTOGENETIC ANALYSIS OF DOG AND HUMAN CHOROID PLEXUS TUMORS DEFINES SYNTENIC REGIONS OF GENOMIC LOSS

Choroid plexus tumors (CPTs) occur spontaneously in humans and dogs providing an opportunity for comparative cross species analysis of common tumor mechanisms. Large scale chromosomal copy number alterations are the hallmark of human CPTs and identification of driver genes within these regions is problematic. Copy number alterations in 12 spontaneous dog CPTs were defined using an Illumina 170K single nucleotide polymorphism array and were characterized by highly recurrent whole chromosomal losses in up to 100% of cases with few chromosome wide gains. Loss of canine chromosomes 2, 5, 8, and 20 were seen in 90%-100% of cases and included regions syntenic to loci within commonly reported whole chromosome losses in human choroid plexus tumors. These regions included previously defined tumor suppressor clusters on chromosome 3p and 17p as well as genes associated with chromosomal instability such as TP53 and VHL. This karyotypic signature is similar to a previously defined hypodiploid subgroup of human choroid plexus carcinomas. The nonrandom, highly recurrent alterations in dog CPTs suggest specific selection pressures and oncogenic mechanisms are present. More extensive analysis of this spontaneous tumor model is warranted and may provide key insights into driver mechanisms common to both species.