Mutation of the p53 tumor suppressor gene in spontaneously occurring osteosarcomas of the dog

Inactivation of the p53 tumor suppressor gene has been implicated in thepathogenesis of numerous human cancers, including osteosarcomas.Appendicular osteosarcomas of the dog appear to be a good model for theirhuman equivalent with regard to biologic behavior, epidemiology andhistopathology. We individually screened exons 5-8 of the p53 gene formutations in 15 canine appendicular osteosarcomas using 'Cold' SSCP tocompare the role of this gene in human and canine osteosarcomatumorigenesis. Seven of the tumors (47%) exhibited point mutations, withone tumor possessing two mutations within different exons. Of these, sevenwere missense mutations and the eighth was a 'silent' mutation potentiallyaffecting the exon 6-7 splicing region. Five of the missense mutations werelocated in highly conserved regions IV and V, while another correspondedwith the highly conserved codon 220 mutational hotspot located outside theconserved domains. The locations and types of mutations were nearlyidentical to those reported in human cancer. These findings provide strongevidence of the involvement of p53 mutations in the development of canineappendicular osteosarcomas. Canine osteosarcomas appear to be a promisingmodel for their human equivalent on a clinical, pathologic, and molecularlevel.