Bladder cancer: Allelic deletions at and around the retinoblastoma tumor suppressor gene in relation to stage and grade

Inhibition of the retinoblastoma tumor suppressor gene (RB) is probably imp ortant in the pathogenesis of urinary bladder cancer. Little information is available concerning allelic loss on 13q11 to 13q32 and its relation to gr ade and stage. In a population-based study, freshly frozen tissue was colle cted from all new cases of urinary bladder cancer in the Stockholm region d uring 1995-1996, Here we report the occurrence of loss of heterozygosity (L OB) at seven sites in 13q11 to 13q32 as analyzed in 236 cases by a fluoresc ent multiples PCR-based on tumor DNA and peripheral blood. For each site, a bout 30% of the cases were not informative because of homozygosity. Replica tion errors were detected in 4% (17 cases), LOH was found in 21 (at 13q11-1 2.1) to 32% (at 13q14.3 in RE) of the informative cases. A correlation was found between the prevalence of LOH at all observed loci and stage and grad e, respectively, and it was statistically significant for 13q14.3. LOB at R B mas found in T-a as well as grade 1 tumors. Also, a statistically signifi cant correlation was found between the number of loci with LOH at 13q and t umor stage and grade, respectively, Typically an altered RE function is rel ated to the expected clinical course of urinary bladder cancer, but allelic loss including the gene also occurs in low grade and low stage tumors. An altered RE function probably is not necessary for a malignant transformatio n of urothelial cells. The causal direction of the relation between the qua ntity of the deleted DNA and tumor aggressiveness is not clear.