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Karyotypic Evolution of a Human Undifferentiated Large Cell Carcinoma of the Lung in Tissue Culture¹

Cancer Cell Biology and Genetics Laboratory, Allegheny-Singer Research Institute, Pittsburgh, Pennsylvania 15212 [D. R. B., S. E. S., A. A. P., C. A. S., K. A. B.]; Department of Obstetrics/Gynecology, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212 [D. M. K., H. R. G.]; Department of Microbiology/Immunology, The Medical College of Pennsylvania, Philadelphia, Pennsylvania 19129 [B. S. S.]

Serial cytogenetic studies were performed on a cell line derived from a pleural effusion from a patient with undifferentiated large cell carcinoma of the lung. The initial sample had a broad range of chromosome numbers per cell, with a hypodiploid/pseudodiploid stem line and a hypotetraploid sideline. A sequence consisting of a doubling of chromosome number per cell followed by chromosome loss was observed repeatedly during 40 culture passages. The presence of metaphase spreads showing evidence of endoreduplication suggested this as a likely mechanism for the doubling of chromosome number per cell. Eleven marker chromosomes were observed in the cells of the primary sample; these markers persisted through all subsequent passages. Chromosomes 1, 2, 6, 7, 8, 11, and 16 were consistently overrepresented; each of these chromosomes was involved in marker formation. Chromosomes 4, 5, 9, 10, 19, 21, and 22 were consistently underrepresented. Every chromosome, either in its normal form and/or as part of a marker, was represented on the average by at least one copy per diploid cell. Eighteen new marker chromosomes were observed during the course of cell cultivation; one of these evolved into a clonal marker over the course of six cell passages. Of the new marker chromosomes that were formed during the observation period, the majority were found in hypotetraploid cells.

¹ Supported by Allegheny-Singer Research Institute.

² To whom requests for reprints should be addressed, at Cancer Cell Biology and Genetics Laboratory, Allegheny-Singer Research Institute, 320 E. North Avenue, Pittsburgh, PA 15212.

Received 8/ 8/88. Revised 3/ 6/89. Accepted 3/22/89.

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