title: Molecular pathogenesis of lung cancer and potential translational applications.
abstract: Molecular studies of lung cancer using individual genes and global approaches of gene analysis have shown several observations that are ready to be translated into clinically useful information to provide new methods of diagnosis, risk assessment, prevention, and treatment. Clinically evident lung cancers have acquired 20 or more clonal genetic alterations, and tumor acquired promoter hypermethylation is a frequent epigenetic mechanism of inactivation of gene expression in lung cancer giving at least another 10-20 lesions. Furthermore, small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) have acquired different genetic and epigenetic lesions. Alterations in 3p tumor suppression genes (TSGs) appear especially early, including those of RASSF1A and SEMA3B at 3p21.3, followed by changes in 9p (p16), 8p, and then multiple other sites. Changes consistent with oxidative damage leading to mitotic recombination are frequently seen. Smoking-damaged, histologically normal epithelium as well as epithelium with preneoplastic/preinvasive changes have thousands of clonal patches containing genetic alterations. Finally, correcting even single genetic abnormalities can reverse the malignant phenotype.
authors.affiliation: Hamon Center for Therapeutic Oncology Research, Department of Internal Medicine, Unversity of Texas, Dallas 75390-8593, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Minna
authors.forename: Kwun
authors.initials: K
authors.lastname: Fong
authors.forename: Sabine
authors.initials: S
authors.lastname: Zöchbauer-Müller
authors.forename: Adi F
authors.initials: AF
authors.lastname: Gazdar
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics; D009857:Oncogenes / Q000235:genetics
chemical_list: D005819:Genetic Markers