K-ras oncogene activation in lung adenocarcinomas from former smokers. Evidence that K-ras mutations are an early and irreversible event in the development of adenocarcinoma of the lung

摘要: Background. Point mutations in codon 12 of the K-ras protooncogene occur more frequently lung adenocarcinomas from smokers (30%) than they do nonsmokers (7%), suggesting that smoking is an important factor induction these mutations. The lack well defined “early” premalignant or situ glandular neoplasms lung, however, has not permitted direct evaluation chronology ras activation development adenocarcinomas. To circumvent need to evaluate precursor lesions, we examined former for point K-ras. Methods. Mutations were detected using polymerase chain reaction amplification and mutation-specific oligonucleotide probes. types frequencies found obtained 57 compared those 27 patients who never smoked current smokers. Results. overall prevalence (32%) was different seen (30%, P = 0.83), greater (7%, 0.015). This pattern independent duration abstinence smoking. Furthermore, predominant type mutation tumors a guanine-to-thymine transversion, specific induced by benzo(a)pyrene, one chemical carcinogens tobacco smoke. Conclusions. These findings support previous suggest oncogene may be target mutagenic activity smoke, DNA alterations at this site can early irreversibly during lung.