MUTATIONS OF THE P53 GENE IN CANINE LYMPHOMA AND EVIDENCE FOR GERM-LINE P53 MUTATIONS IN THE DOG

Mutations of the p53 gene are associated with a number of non-lymphoid cancers of the dog. The present study investigates the p53 gene statu s within canine patients treated for primary and secondary lymphoma. T hree out of eight patients exhibited p53 gene mutations, These include d one patient with a germ line mutation and two patients with de novo p53 mutations associated with the secondary lymphoma. Allelic loss of the p53 gene was also observed within primary and secondary tumours of the three canine patients. The results indicate that germ line p53 mu tations exist in dogs and may be involved in the known predisposition of some breeds to cancer, The presence of therapy-related p53 point mu tations was found to be associated with chemoresistant secondary lymph omas. A causative role for DNA-damaging chemotherapy in de novo mutati on of the p53 gene is discussed, Characterization of p53 inactivation in canine tumorigenesis may provide a valuable clinical model for asse ssing the efficacy and optimal therapeutic regimens of anti-cancer age nts.