Allelic losses demonstrate monoclonality of multifocal bladder tumors

Int J Cancer. 2000 Aug 15;87(4):522-7.


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 monoclonality of the patients' tumors. No allelic imbalancies were detected between heterozygote alleles, and the allelic losses were only slightly biased 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 monoclonality using binomial distribution. The use of multiple tumors with multiple microsatellite markers gives high statistical power for the calculation. The combined probabilities for monoclonality varied from 0.984 to (1-4 x 10(-28)). Thus, in most (4/5) cases, the probability for polyclonality was <2 x 10(-16). These results demonstrate that superficial multifocal bladder tumors are most likely of monoclonal origin.

MeSH terms

  • Alleles*
  • Carcinoma, Transitional Cell / blood
  • Carcinoma, Transitional Cell / genetics*
  • Carcinoma, Transitional Cell / pathology
  • Chromosomes, Human
  • Clone Cells / pathology
  • DNA, Neoplasm / blood
  • Fluorescence
  • Humans
  • Leukocytes / chemistry
  • Loss of Heterozygosity
  • Microsatellite Repeats
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasms, Multiple Primary / blood
  • Neoplasms, Multiple Primary / genetics*
  • Neoplasms, Multiple Primary / pathology
  • Polymerase Chain Reaction
  • Urinary Bladder Neoplasms / blood
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology


  • DNA, Neoplasm