Identification of Frequent Novel Genetic Alterations in Small Cell Lung Carcinoma

We have performed a comprehensive analysis of the DNA copy number changes that occur in 18 small cell lung carcinoma cell lines using comparative genomic hybridization (Kalliomemi et aL, Science (Washington DC), 258: 818-821, 1992). DNA copy number abnormalities detected in this study include previously identified increases at lp22-32 (L-myc), 2p24-25 (N-myc), and 8q24 (c-myc) and decreases at 17pl3 (p53),13ql4 (RB) and 3p. In addition, novel DNA copy number increases were detected at 5p, lq24, and Xq26, and novel decreases were found at 22ql2.1-13.1, 10q26, and 16pll.2. Many of the most common DNA copy number changes revealed are at loci not previously recognized to be important in small cell lung cancer. In addition, a number of the DNA copy number changes, including increases at lp22-32, 2p24-25, and 3q22-25 and a decrease on 18p, were found to occur preferentially in small cell lung carcinoma lines of the “variant” phenotype. This correlation suggests that genes may reside at these tod whose overexpression or inactivation contributes to the radiation resistance or aggressive growth phenotypes characteristic of this subtype of small cell lung carcinoma.