SIMILAR INCIDENCE OF K-RAS MUTATIONS IN LUNG CARCINOMAS OF FVB N MICEAND FVB/N MICE CARRYING A MUTANT P53 TRANSGENE/

Mutated p53 genes are capable of complementing activated ras genes in the transformation of primary rat embryo fibroblasts in vitro, Mutatio ns in both genes have also been found in several human cancers, includ ing lung carcinomas, We generated transgenic mice containing a p53 con struct with a missense mutation in exon 5 (ala135val) to study the rol e of p53 mutations in lung tumorigenesis, and to facilitate identifica tion of other genetic events that might complement p53 mutations in mo use lung carcinogenesis, The p53 transgenic lines exhibited a higher f requency of lethal lung tumors than the parental FVB/N strain, We exam ined the spontaneously-arising lung carcinomas from mice expressing th e mutated p53 transgene for K-ras mutations using single-stranded conf ormation polymorphism (SSCP) and/or direct sequencing approaches, Fift een of 29 (52%) carcinomas contained mutations in the K-ras oncogene, Six of 15 of the K-ras mutations were in codon 61 and 9/15 were in cod on 12, Subsequent analysis of spontaneous lung carcinomas from mice of the FVB/N parental strain showed that 9/12 (75%) carcinomas examined contained K-ras mutations, Two of these were in codon 12, one in codon 13, and 6 were in codon 61, These results demonstrate that the freque ncy of ras mutations does not differ between the p53 FVB/N transgenic mice and their parental FVB/N strain but suggest that a high frequency of mutations K-ras can be correlated with lung tumorigenesis in both groups of mice.