Inactivation of MMAC1 in bladder transitional-cell carcinoma cell lines and specimens

We recently limited the location of a candidate tumor suppressor gene in in vasive (T3a/b) bladder transitional-cell carcinoma (TCC) to a 2.5-cM region at chromosome 10q23.3. This region harbors the MMAC1/PTEN/TEP1 gene (refer red to hereafter as MMAC1), a dual-phosphatase tumor-suppressor gene freque ntly inactivated in variety of malignant tumors. In the present study, we e xamined whether MMAC1 is a target for inactivation by mutations and deletio ns in bladder TCC cell lines and specimens. MMAC1 was inactivated by homozy gous deletions and mutations in three (27%) of 11 bladder cancer cell lines . One cell line, UC-3, had homozygous deletions, and two other cell lines, T-24 and UC-9, had missense mutations. T-24 had also a nonsense mutation. H owever, none of the 33 bladder TCC specimens examined had a mutation or del etion in the coding region. These results suggest that MMAC1 is not the pri mary target for inactivation in bladder TCC and that another gene, in close proximity to the MMAC1 locus, within this region of frequent allelic losse s, may be the target for inactivation. (C) 2000 Wiley-Liss, Inc.