CODON-12 KI-RAS MUTATION IN NON-SMALL-CELL LUNG-CANCER - COMPARATIVE-EVALUATION IN TUMORAL AND NONTUMORAL LUNG

Ki-ras activation by point mutation on codon 12 has been reported in n on-small-cell lung carcinomas and in various models of experimental lu ng tumours induced by chemical carcinogens. The cellular targets for c arcinogenic compounds of tobacco smoke are usually considered to be th e cells of the bronchial mucosa or alveolar epithelium. However, littl e is known about preneoplastic events in bronchopulmonary carcinogenes is. The hypothesis of the presence of widespread target cells containi ng Ki-ras mutation was investigated by evaluating concurrent neoplasti c and non-neoplastic bronchial and alveolar samples from 51 patients w ith non-small-cell lung carcinomas. The polymerase chain reaction-rest riction fragment length polymorphism (PCR-RFLP) method used can detect one cell with a mutation on codon 12 among 10(2) normal cells. In tum our samples, a mutation was detected in 20% of adenocarcinomas, but in none of the adenosquamous or squamous cell carcinomas. No mutation wa s detected in the non-neoplastic bronchial or parenchymal samples. Whe n using an enriched PCR-RFLP method detecting one mutated allele among 10(3) normal alleles a mutation was detected in 23% of adenocarcinoma s. In conclusion, Ki-ras activation by mutation on codon 12 was not ob served in non-neoplastic bronchial or parenchymal tissues in patients with bronchopulmonary cancers and does not appear to be a genetic even t present in non-malignant epithelial target cells exposed to tobacco smoke.