Characteristic Genetic Alterations in Lung Cancer

Lung cancer is the most frequent cause of cancer deaths in both men and women in the U.S. (1 ). Although tobacco smoking is accepted as the number one cause of this devastating disease, our understanding of the acquired genetic changes leading to lung cancer is still rudimentary. Lung cancer is classified into two major clinic-pathological groups, small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) (2 ). Squamous cell carcinoma, adenocarcinoma, and large cell carcinoma are the major histologic types of NSCLC. As with other epithelial malignancies, lung cancers are believed to arise after a series of progressive pathological changes (preneoplastic lesions) (3 ). Many of these preneoplastic changes are frequently detected accompanying lung cancers and in the respiratory mucosa of smokers (3 ). Although many molecular abnormalities have been described in clinically evident lung cancers (4 ), relatively little is known about the molecular events preceding the development of lung carcinomas and the underlying genetic basis of tobaccorel ated lung carcinogenesis.