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Delineation of the 6p22 Amplification Unit in Urinary Bladder Carcinoma Cell Lines¹

Department of Medical Genetics [J. B., J. H., R. K., W. V., H. H.] and Department of Pathology [I. M., S. B., P. M., R. K.], University Ulm, Albert-Einstein-Allee 11, D-89069 Ulm, Germany; and Department of Urology, Heinrich-Heine-University Düsseldorf, Moorenstraße 5, D-40225 Düsseldorf, Germany [W. A. S.]

Eight cell lines from transitional cell carcinoma of the urinary bladder were analyzed by comparative genomic hybridization. All tumor lines exhibited frequent chromosome gains (11.5/cell line) and losses (8.4/cell line). In six cell lines, gain of chromosome 5p was associated with gains of 6p and 20q. In five of these cell lines, amplification of parts of 6p was observed. Cytogenetic investigation combined with fluorescence in situ hybridization analysis revealed typical marker chromosomes with homogeneously staining regions (HSRs) containing material from 6p. By hybridizing individual yeast artificial chromosome probes from a chromosome 6p contig to these HSRs, a contig of three yeast artificial chromosomes common to all 6p HSRs was identified that spans less than 2 Mb. The genes SOX4 and PRL were shown to map to this region and to be coamplified in the cell lines. However, SOX4 was not overexpressed in any cell line and PRL was not expressed at all. Thus, the presumptive 6p oncogene remains to be conclusively identified.

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