TAILIEUCHUNG - Lung Cancer Edited by Barbara Driscoll Volume I Molecular Pathology Methods and Reviews Lung Cancer Edited by Barbara Driscoll Volume I Molecular Pathology Methods and Reviews

Lung cancer is the most frequent cause of cancer deaths in both men and women in the . (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 classifi ed 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 | 1__ Characteristic Genetic Alterations in Lung Cancer Ignacio I. Wistuba and Adi F. Gazdar 1. Introduction Lung cancer is the most frequent cause of cancer deaths in both men and women in the . 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 tobacco-related lung carcinogenesis. To investigate the molecular abnormalities involved in the multistep pathogenesis of lung carcinomas we have developed a five-step analysis scheme that included the study of 1 lung cancer cell lines 2 microdissected primary lung tumors of the three major histologic types SCLC squamous cell carcinoma and adenocarcinoma and normal and abnormal respiratory epithelium from 3 lung cancer patients 4 from smoker subjects without lung cancer and from 5 never smoker subjects see Fig. 1 . Under this strategy we systematically search for mutations in tumor cell-lines specimens and in archival tumor tissues preneoplastic lesions and normal epithelium using paraffin-embedded From Methods in Molecular Medicine vol. 74 Lung Cancer Vol. 1 Molecular Pathology

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