Two target regions of allelic loss on chromosome 9 in urinary-bladder cancer.

Allelic losses on chromosome 9 are common in a wide variety of human tumors; moreover, two predisposing loci for some inherited cancer syndromes, i.e., familial malignant melanoma and Gorlin syndrome, have been identified on this chromosome. To define the location of putative tumor suppressor genes involved in cancer of the urinary bladder, 85 bladder cancers were examined for allelic loss at 18 microsatellite loci on chromosome 9. Correlations were also sought between loss of heterozygosity on chromosome 9 and several clinicopathological parameters. Allelic loss was observed in 54 of the tumors (64%) and deletion mapping identified two target regions; one at an interval on 9p21 flanked by D9S736 and D9S165, and the other at an interval on 9q31-34 flanked by D9S58 and D9S61. No subtle mutation was detected in the PTCH gene which lies in the latter interval. Allelic loss on chromosome 9 was observed frequently in low grade and non-invasive tumors as well as in tumors of more advanced phenotype. Inactivation of tumor suppressor genes lying in either of two regions of common deletion identified on chromosome 9 might affect carcinogenic mechanisms at an early stage of tumor development in the urinary bladder.