DETECTION OF CHROMOSOMAL IMBALANCES IN TRANSITIONAL-CELL CARCINOMA OFTHE BLADDER BY COMPARATIVE GENOMIC HYBRIDIZATION

Comparative genomic hybridization (CGH) was applied for a comprehensiv e screening of chromosomal aberrations in 14 transitional cell carcino mas of the bladder of different grade and stage. The results were comp ared in a number of selected Crises with those obtained by restriction fragment length polymorphism analyses and targeted fluorescence in si tu hybridization. Distinct amplifications,found with CGH, were located on 3p22-24, 10p13-14, 12q13-15, 17q22-23, 18p11, and 22q11-13. These high copy number amplifications and the frequency of imbalances involv ing chromosome 5, occurring in 4 of 14 cases, have not yet been identi fied in transitional cell carcinomas. Apart from these new aberrations , imbalances were detected in 3 or more cases for chromosomes 3 and II , as already described previously In the literature. In four tumors, t he copy number of specific chromosomal regions was also analyzed by in terphase cytogenetics. Although in most instances the CGH data were co nfirmed, in one tumor, distinct differences were observed, possibly a result of heterogeneity of the tumor cell population. Furthermore, the CGH data were compared with loss of heterozygosity as revealed by res triction fragment length polymorphism analysis in the same tumors. In 80% of informative cases, no loss was detected by restriction fragment length polymorphism or by CGH. Of the 15 cases of loss of heterozygos ity, 7 showed a loss also with CGH, whereas in 8 cases no loss was obs erved In summary, CGH is a fast method to obtain a comprehensive pictu re of chromosomal imbalances in transitional cell carcinomas, includin g a number of previously unknown genomic alterations such as high leve l amplifications.