HOMOZYGOUS DELETIONS WITHIN CHROMOSOMAL BANDS 9P21-22 IN BLADDER-CANCER

The loss of DNA sequences on chromosomal bands 9p21-22 has been docume nted in a variety of malignancies including leukemias, gliomas, lung c ancers, and melanomas. Because of the high incidence of monosomy S det ected by both cytogenetics and loss of heterozygosity studies in bladd er cancer, we examined seven bladder cancer cell lines for deletions i n this region. Using seven DNA probes that span the region of 9p21-22 as well as a functional assay for methylthioadenosine phosphorylase (M TAP), which maps to 9p21, we found four cell lines that had small homo zygous deletions. These deletions map centromeric to the interferon (I FN) gene cluster and telomeric to D9S171. Only one of the cell lines w ith deletions had a cytogenetically evident lesion in this chromosomal region. Preliminary loss of heterozygosity studies with 10 primary bl adder cancer specimens using 10 markers spanning chromosome 9 revealed loss of heterozygosity at the IFN locus with retention of heterozygos ity with more centromeric 9p markers and all informative 9q markers in the tumor of one patient. These data suggest that loss of a tumor sup pressor gene on 9p21-22, which may represent a general pathway of onco genesis, is important in bladder cancer development.