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Chromosome Alterations in Human Small Cell Lung Cancer: Frequent Involvement of 5q¹

Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111 [I. M., J. Q. C., J. R. T.]; Department of Medicine, State University of New York-Health Science Center and Veterans Administration Medical Center, Syracuse, New York 13210 [S. L. G.]; and University of Maryland Cancer Center, Baltimore, Maryland 21201 [L. A. D.]

Deletions of the 3p chromosome region and molecular alterations of the tumor suppressor genes RB1 and TP53, located, respectively, at 13q14 and 17p13, are well-documented in small cell lung cancer (SCLC). Because of technical difficulties, karyotypes of primary SCLC specimens are rarely reported. In this study, detailed cytogenetic analysis was performed on 13 early passage SCLC cell lines and fresh specimens, including 4 lung primaries. Numerous chromosome alterations were found, even in newly diagnosed primary tumors. Consistent with previous molecular studies, chromosomal losses of 3p (13 cases) and 17p13 (12 cases) were frequently observed. Numerical losses of chromosome 13 and structural rearrangements affecting 13q14 were identified in 10 specimens. In addition, losses of chromosome 5 and structural alterations of 5q occurred in 12 tumors; among these, 9 displayed losses of region 5q13–q21. Double minutes were found in 4 cases (3 of 5 specimens from patients who received prior cytotoxic therapy but only 1 of 8 from untreated patients). DNA analysis revealed amplification of either MYC1 or MYCN in cells from each of these 4 tumors. Overall, the cytogenetic findings underscore that progression of SCLC involves multiple genetic changes and suggest further that a tumor suppressor gene(s) on 5q may contribute to SCLC tumorigenesis.

¹ This work was supported by NIH Grants CA-45745 and CA-06927 and by an appropriation from the Commonwealth of Pennsylvania. Research support to S.L.G. was provided by a Clinical Oncology Career Development Award of the American Cancer Society and the Veterans Administration Research Service. Part of this work was performed while J.R.T. was a Scholar of the Leukemia Society of America.

² To whom requests for reprints should be addressed, at Section of Molecular Cytogenetics, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111.

Received 9/20/91. Accepted 12/13/91.

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