Rapid detection of K-ras gene mutations in canine lung cancer using single-strand conformational polymorphism analysis.

Abstract

A total of 126 spontaneous lung tumors from pet dogs were examined for K-ras mutations within exon 1 and exon 2 using a non-radioisotope single-strand conformational polymorphism analysis (SSCP) detection method 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 cell carcinomas (3) and anaplastic carcinomas (9). Nineteen mutations were detected in the malignant tumors: 18 occurred in exon 1 codon 12 and one in exon 2 codon 61. No mutations were present in the adenomas. The most common mutation was a G-->A transition (11/19) in the second position of codon 12. Based on this study, K-ras mutations occur in canine non-small cell lung carcinomas. The frequency and type of mutation more closely matches tumors from human non-smokers with K-ras mutations than smokers. With the application of screening techniques such as SSCP, large numbers of dog tumors can be examined to provide a large animal model for comparative studies of carcinogenesis.