Allelic losses demonstrate monoclonality of multifocal bladder tumors

The clonality of multifocal bladder tumors has been studied over the years with some controversial results. We have examined 5 patients with 2-11 low- grade superficial multifocal bladder tumors for loss of heterozygosity (LOH ) at 87 loci on 9 chromosomes. When LOH was detected at a given marker, the tumors consistently showed deletion of a specific allele, suggesting the m onoclonality of the patients' tumors. No allelic imbalancies were detected between heterozygote alleles, and the allelic losses were only slightly bia sed toward the loss of the shorter alleles as the overall ratio was 0.48 +/ - 0.10 (0.50 for nonbiased). We calculated the probabilities for monoclonal ity using binomial distribution. The use of multiple tumors with multiple m icrosatellite markers gives high statistical power for the calculation. The combined probabilities for monoclonality varied from 0.984 to (1-4 x 10(-2 8)). Thus, in most (4/5) cases, the probability for polyclonality was <2 x 10(-16). These results demonstrate that superficial multifocal bladder tumo rs are most likely of monoclonal origin. Int. J. Cancer 87:522-527, 2000. ( C) 2000 Wiley-Liss, Inc.