CHROMOSOMAL CHANGES DURING PROGRESSION OF TRANSITIONAL-CELL CARCINOMAOF THE BLADDER AND DELINEATION OF THE AMPLIFIED INTERVAL ON CHROMOSOME ARM 8Q

The cascade of genetic alterations leading to malignant transformation has been described for adenocarcinoma of the colon but is not establi shed for other common tumor entities. In the present study, different stages of transitional cell carcinoma (TCC) of the bladder are analyze d by comparative genomic hybridization. A dynamic pattern of the chrom osomal changes during tumor progression is described. Deletion of chro mosome arm 9q is the earliest genetic alteration in pTa tumors. In sta ge pTl carcinomas, losses of 9q, 9p, and 11p and gain of 1q and 8q are the most common. In addition to the changes specific for earlier stag es, gain of 5p and 20q becomes prominent in carcinomas stage greater t han or equal to pT2. Association analysis reveals a remarkable cooccur rence of 9p deletion with gain of 5p and 20q in greater than or equal to pT2 tumors. In order to determine more precisely the size of the am plified segment and the degree of amplification on chromosome arm 8q i n stage pTl tumors, this region was analyzed by semiquantitative PCR u sing polymorphic microsatellite markers. These studies revealed an up to 13-fold amplification. The common region of amplification could be narrowed down to 8q22.3 and between GAATIA4 and D8S1834 (about 7 cM). (C) 1998 Wiley-Liss. Inc.