Abstract
The general aim of this work was to investigate the clonality of
multifocal bladder tumours, chromosomal deletions and model the
initiation-progression of bladder tumours at a molecular level using
microsatellite analysis. In a population-based study, we found
correlation between stage and grade and the prevalence of loss of
heterozygosity (LOH) at all observed chromosome 13 loci and stage and
grade, respectively. Statistically significant correlation was found for
13q14.3, the Rb locus, and between the number of loci with LOH at 13q and
tumour stage and grade, respectively. Clonality was studied using
superficial multifocal bladder tumours. The given patient had always lost
the same microsatellite allele when LOH was encompassed, suggesting
monoclonality of the tumours. In the majority of the cases the
polyclonality was excluded with at least 1-2x10-16 probability,
calculated using binomial distribution. At chromosome 9, at least three
consensus regions were found to be deleted at superficial multifocal
bladder tumours, one at 9p (9p21-22) and two at 9q (9q21-22 and 9q32-34).
All the regions appeared to be equally important and during the
development of tumours all these regions were finally affected. At
chromosome 3 at three loci on chromosome 3p25-26, 3p14.2 and 3q27 had
frequent LOH in multifocal superficial bladder tumours. The
phylogenetic-type analysis suggested that the FHIT region at 3p14.2
contain often the very first alterations at chromosome 3. The
tumour-adjacent surrounding tissues were found to contain similar
alterations as the tumour tissues. On chromosome 9 all the patients
analysed showed LOH in at least one surrounding sample and over 60% of
them showed LOH also on chromosome 3. On chromosome 9 three distinct
clusters of LOH were found, 9p21-22, 9q13-22 and 9q31-34.2 and at
chromosome 3p (D3S3050) and at 3q27 (D3S2418).
