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 t he pathogenesis of numerous human cancers, including osteosarcomas. Ap pendicular osteosarcomas of the dog appear to be a good model for thei r human equivalent with regard to biologic behavior, epidemiology and histopathology, We individually screened exons 5-8 of the p53 gene for mutations in 15 canine appendicular osteosarcomas using 'Cold' SSCP t o compare the role of this gene in human and canine osteosarcoma tumor igenesis, Seven of the tumors (47%) exhibited point mutations, with on e tumor possessing two mutations within different exons, Of these, sev en were missense mutations and the eighth was a 'silent' mutation pote ntially affecting the exon 6-7 splicing region, Five of the missense m utations were located in highly conserved regions IV and V, while anot her corresponded with the highly conserved codon 220 mutational hotspo t located outside the conserved domains, The locations and types of mu tations were nearly identical to those reported in human cancer, These findings provide strong evidence of the involvement of p53 mutations in the development of canine appendicular osteosarcomas, Canine osteos arcomas appear to be a promising model for their human equivalent on a clinical, pathologic, and molecular level.