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Identification of Frequent Novel Genetic Alterations in Small Cell Lung Carcinoma¹

Department of Radiation Oncology [N. A. L., P. B., N. G., J. W. G., M. F. C.] and Division of Molecular Cytometry in the Department of Laboratory Medicine [N. A. L., N. G., J. W. G.], University of California, San Francisco, California 94143, and Simmons Cancer Center, University of Texas, Southwestern Medical Center, Dallas, Texas 75235 [J. D. M.]

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 (Kallioniemi et al., Science (Washington DC), 258: 818–821, 1992). DNA copy number abnormalities detected in this study include previously identified increases at 1p22–32 (L-myc), 2p24–25 (N-myc), and 8q24 (c-myc) and decreases at 17p13 (p53), 13q14 (RB), and 3p. In addition, novel DNA copy number increases were detected at 5p, 1q24, and Xq26, and novel decreases were found at 22q12.1–13.1, 10q26, and 16p11.2. 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 1p22–32, 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 loci whose overexpression or inactivation contributes to the radiation resistance or aggressive growth phenotypes characteristic of this subtype of small cell lung carcinoma.

¹ This work was performed using the facilities of the LBL/UCSF Resource for Molecular Cytogenetics and is supported by both the United States Department of Energy under contract DE-AC-03-76SF00098 and Imagenetics. N. G. is a Research Fellow of the Medical Research Council of Canada.

² To whom requests for reprints should be addressed, at Department of Radiation Oncology, University of California at San Francisco, 1855 Folsom Street, MCB200, Box 0806, San Francisco, CA 94103.

Received 5/ 4/94. Accepted 8/ 4/94.

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