Localization of tumor suppressor gene associated with distant metastasis of urinary bladder cancer to a 1-Mb interval on 8p22.

To identify the location of one or more putative tumor suppressor genes that may be involved in urinary bladder cancer, we examined 82 such tumors for allelic losses at 19 microsatellite loci on 8p. Loss of heterozygosity was observed in 31 of the cases. Deletion mapping identified a commonly deleted region at 8p22, within the 1-Mb interval flanked by D8S1135 and AFM177XB10. Allelic loss at 8p22 was associated with higher tumor grade (17/31, 55%, vs. 12/51, 23%; P = 0.0013). Furthermore, no tumor that retained heterozygosity for markers at 8p22 had metastasized to distant organs, whereas a substantial portion of tumors that lost alleles in that region had done so (0/51, 0%, vs. 6/31, 20%; P = 0.001). These data imply that loss or inactivation of tumor-suppressing activity encoded on 8p contributes to malignancy and to the metastatic potential of bladder cancers.