Initiation-development modelling of allelic losses on chromosome 9 in multifocal bladder cancer

Multiple low-grade, low-stage superficial tumours were analysed for loss of heterozygosity (LOH) on chromosome 9 with 29 markers. Three consensus regions were found, one at 9p (9p21-22) and two at 9q (9q21-31 and 9q32-34). Phylogenetic trees were calculated for each patient using both designated chromosome 9 regions and, separately, using individual microsatellite data. Regional analysis suggested that multiple, equally important regions for bladder tumour initiation exist on chromosome 9. During the development of tumours all regions were eventually affected. The phylogenetic analyses with individual markers were used as molecular clocks to trace the ordering of tumours. The results were compared with the physical locations of the tumours and a hypothetical development model was built. These are novel approaches which, to our knowledge, have not been used before.