Identification of tumour-associated and germ line p53 mutations in canine mammary cancer

Mutations of the tumour suppressor p53 gene are found in a number of sponta neous canine cancers and may contribute to increased cytogenetic alteration s and tumour formation. Using reverse transcription and DNA amplification, we isolated p53 cDNA from normal and tumour tissue of ten canine mammary ca ncer patients. DNA sequencing identified p53 mutations in three of the ten patients. These included tumour-associated p53 gene mutations within exons 2 and 5 and a germ line deletion of exons 3 to 7. These results support a r ole for p53 inactivation in canine mammary tumour formation and breed predi sposition to cancer. Such information could prove invaluable in the success ful outbreeding of inherited predisposition to cancer in the dog. A putativ e polymorphism was also identified at codon 69 in exon 4 and we discuss the possibility that similar polymorphisms may be associated with human breast cancer. (C) 1999 Cancer Research Campaign.