RAPID DETECTION OF K-RAS GENE-MUTATIONS IN CANINE LUNG-CANCER USING SINGLE-STRAND CONFORMATIONAL POLYMORPHISM ANALYSIS

A total of 126 spontaneous lung tumors from pet dogs were examined for K-ras mutations within exon I and exon 2 using a non-radioisotope sin gle-strand conformational polymorphism analysis (SSCP) detection metho d on PCR products, Mutations were confirmed by direct DNA sequencing. Tumors were classified as adenomas (9), bronchioloalveolar carcinomas (59), adenocarcinomas (30), adenosquamous carcinomas (16), squamous ce ll carcinomas (3) and anaplastic carcinomas (9). Nineteen mutations we re detected in the malignant tumors: 18 occurred in exon 1 codon 12 an d one in exon 2 codon 61, No mutations were present in the adenomas. T he most common mutation was a G-->A transition (11/19) in the second p osition of codon 12, Based on this study, K-ras mutations occur in can ine non-small cell lung carcinomas. The frequency and type of mutation more closely matches tumors from human non-smokers with K-ras mutatio ns than smokers. With the application of screening techniques such as SSCP, large numbers of dog tumors can be examined to provide a large a nimal model for comparative studies of carcinogenesis.