CHROMOSOME-9 ALLELIC LOSSES AND MICROSATELLITE ALTERATIONS IN HUMAN BLADDER-TUMORS

Chromosome 9 allelic losses have been reported as a frequent and early event occurring in bladder cancer. It has been postulated that a cand idate tumor suppressor gene may reside on this chromosome, alterations of which may lead to the development of a subset of superficial bladd er tumors. More recently, the involvement of two different regions har boring suppressor loci, one on each of bath chromosome 9 arms, has bee n proposed. We undertook the present study with the objectives of bett er defining the deleted regions of chromosome 9 in bladder tumors, as well as evaluating the frequency of microsatellite alterations affecti ng certain loci on this chromosome in urothelial neoplasia. Seventy-th ree primary bladder tumors were analyzed using a set of highly polymor phic markers, and results were correlated with pathological parameters associated with poor clinical outcome. We observed that, overall, 77% of the tumors studied showed either loss of heterozygosity for one or more chromosome 9 markers and/or microstellite abnormalities at chrom osome 9 loci. Detailed analyses showed that two regions, one on 9p at the interferon cluster, and the other on 9q associated with the q34.1- 2 bands, had the highest frequencies of allelic losses. Furthermore, T -a lesions appeared to present mainly with 9q abnormalities, while T-1 tumors displayed a mixture of aberrant 9p and 9q genotypes. These obs ervations indicate that loss of heterozygosity of 9p may be associated with the development of superficial tumors with a more aggressive bio logical behavior or, alternatively, they may be related to early disea se progression. In addition, microsatellite alterations mere documente d in over 40% of amplified cases. Taken together, these data suggest t hat two different tumor suppresser gene loci on chromosome 9 are invol ved as tumorigenic events in bladder cancer and that chromosome 9 micr osatellite alterations are frequent events occurring in urothelial neo plasia.