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Leading physician scientists and noted researchers review novel methods for determining the etiology of a variety of lung cancers and present readily reproducible techniques for examining the associated multitude of genetic abnormalities. The methods make it possible to detect these alterations at the cellular, DNA, and protein levels, to study the development of lung cancer in vitro and in vivo-either in situ or in the form of metastases, and to test targeted therapies with detailed model systems. An animal models section gives explicit instructions for setting up and testing these systems, which are rarely described in the literature.
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M E T H O D S I N M O L E C U L A R M E D I C I N E TM Lung Cancer Volume I Molecular Pathology Methods and Reviews Edited by Barbara Driscoll Humana Press Genetic Alterations 3 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 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 ca