Bladder cancer genotype stability during clinical progression.

Genomic instability is manifested by the accumulation of large numbers of mutations. The rate at which mutations accumulate has been difficult to estimate because serial comparisons are required. For further insight into how quickly mutations accumulate during clinical progression, cell lines sequentially isolated 6 or 11 months apart from two patients with metastatic bladder cancer were compared for loss of heterozygosity (LOH). The genomes were scanned at approximately 200 polymorphic microsatellite loci to increase the resolution and sensitivity for losses. The cell lines from both patients had evidence of genomic instability, with aneuploidy, chromosomal instability, and fractional allelic losses of 0.15 and 0. 48, respectively. However, additional changes were relatively infrequent, with more than 90% identity between the initial and recurrent cell lines. Allelic losses were not randomly scattered, but clustered on specific chromosomes. Therefore, the numbers of loci with further LOH during the clinical progression of some bladder cancers are small relative to the total number of loci with LOH, suggesting that most allelic losses accumulate before clinical presentation. Copyright 2000 Wiley-Liss, Inc.