Status of the p53, Rb and MDM2 genes in canine osteosarcoma

The key role of p53 and Rb alterations in human osteosarcoma is clear. For example, osteosarcoma is common in individuals inheriting mutant p53 or Rb genes. Osteosarcoma in dogs is similar to humans by histology, site,gender ratio and several other biological parameters. To study whether this simila rity extends to the molecular level, 21 canine osteosarcomas were analyzed for alterations of p53, Rb and MDM2. MDM2 is a normal cell protein which an tagonizes p53, amplification is seen in some human sarcomas. The gross stru cture of the p53, Rb and MDM2 genes was examined by Southern blotting. No d eletions or rearrangements of the p53 or Rb genes were detected. The absenc e of gross gene alterations affecting these tumor suppressor genes is a sig nificant difference between the disease in dogs and humans, since rearrange ments ol deletions of the p53 or Rb genes occur in 20-30 per cent of human osteosarcomas. The MDM2 gene appear-ed to be duplicated in one canine tumor but no cases of significant amplification were detected. Expression of nor mal Rb was detected in all cases. Mutations of the p53 gene were found in 3 8 percent of canine osteosarcomas. Analysis of mutations revealed a predomi nance of spontaneous mutation. These finding emphasize the key role that al terations of p53 have in the development of osteosarcoma in dogs and humans .