Potential location of a bladder tumor suppressor gene on chromosome 9q at 9q13 to 9q22.1

Allelic losses involving chromosome 9q occur in a significant percentage of bladder tumors. Experimental evidence suggests that a putative tumor suppressor gene located on this chromosome may play a role in the development of bladder cancer. The precise location of this potential tumor suppressor gene is not clear. Previous studies have targeted a large region between 9p12-13 and 9q22 or 9p12 and 9q34.1 as the likely site. To further delineate the location of this gene, we examined 49 tumors by loss of heterozygosity (LOH) analysis, using seven microsatellite polymorhpic loci spanning from 9p21 to 9q34 of the chromosome. LOH was found in at least one of the loci in 20 (41%) of the tumors examined, and the majority (12 of 17; 71%) of the losses on 9q involved large segments or the entire chromosome arm. Although many of the tumors with large losses on 9q also involved 9p21, several tumors with small losses did not involve the 9p marker. Conversely, there were tumors with 9p21 losses that did not involve the q-arm. These data agree with recent findings that distinct tumor suppressor genes associated with bladder cancer are located on separate arms of chromosome 9. Among tumors with single locus LOHs, the most common deletion was located in 9q 13-21.2, which was detected by probe D9S15. This also is the smallest area of critical loss when LOH patterns of tumors with partial or interstitial losses were examined. Results of the study therefore suggest that a potential tumor suppressor gene may reside within or near the region of 9q13-22.1.