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Evidence for Progressional Changes in the Human Malignant Glioma Line U-343 MGa: Analysis of Karyotype and Expression of Genes Encoding the Subunit Chains of Platelet-derived Growth Factor¹

Department of Pathology, University of Uppsala, University Hospital, S-751 85, Uppsala [M. N., C. B., M. B., M. P., B. Wes.], and Cytogenetic Laboratory, Department of Pathology, Central Hospital, Postbox, S-541 01, Skövde [B. W., J. M.], Sweden

Three cell samples in different passages of the line U-343 MGa, derived from a human malignant glioma biopsy, gave rise to clones with different amounts of platelet-derived growth factor (PDGF)-like activity secreted to extracellular medium, and of ¹²⁵I-labeled PDGF binding. Sixteen clones were completely karyotyped with the G-banding technique. The unique markers 1p-q+, 16p- found in all clones, as well as in the parallel uncloned line, U-343 MG, provided evidence of their common origin. The deduced early, possibly partly primary, deviations had the formula 44, XY, 1p-q+, -14, 16p-, -22, where loss of one chromosome 22 is in accordance with previous reports on early chromosomal deviations in gliomas. Two clones, the hypodiploid 26L and 5H, represented early progressional changes. The other clones followed two patterns of late progressional changes, probably starting from the karyotype of 5H, with additional markers and doubling of the stemlines. In late progressional line I 12q+ and in II +7 were the most characteristic findings.

Northern blot analysis using complementary DNA clones for the A and B chains of PDGF showed that both PDGF chains were expressed in 26L and 5H indicating that activation of the PDGF genes could have been an early event in the development of this glioma. Clones with late progression pattern II had been subjected to the highest selective pressure in vitro, and they secreted the highest amount of PDGF-like activity to the extracellular medium. Among them were the most rapidly and tightly growing cells and some clones with high ¹²⁵I-labeled epidermal growth factor binding. Possibly these findings reflect progressional changes including defective regulation of the growth factor/growth factor receptor genes, selected for in vitro, without involving gross rearrangements or amplifications of the genes. The possible significance of extra chromosomes 7, with the PDGF A chain and epidermal growth factor receptor genes, and of the 12q+ marker, located near the interferon gene is discussed.

¹ This work was supported by grants from the Swedish Cancer Society, Swedish Society of Medical Sciences, and the University of Uppsala.

² To whom requests for reprints should be addressed.

Received 10/ 8/86. Revised 4/24/87. Accepted 4/30/87.