Molecular analysis of PTEN and MXI1 in primary bladder carcinoma

Loss of heterozygosity (LOH) on 10q is associated with late-stage events in urothelial neoplastic progression. The tumor suppressor gene PTEN, which i s mutated or homozygously deleted in numerous cancers, maps to a region of lag within the reported region of minimal loss in bladder tumors. In two re cent studies alterations in the PTEN gene occur at a low frequency in bladd er tumors displaying 10q LOH. We have screened 35 late-stage bladder tumors for mutations in PTEN and MX11, both genes mapping to chromosome 10q, Usin g single-strand conformation polymorphism analysis, we identified 6 tumors harboring mutations in PTEN and 2 additional tumors displaying homozygous d eletion at this locus. No MX11 mutations were identified within the same tu mor panel. Of 16 bladder tumor cell lines analyzed, 2 showed homozygous del etion of PTEN and 3 harbored point mutations resulting in an amino acid cha nge. Two cell lines harbored missense mutations in MX11. We report a signif icantly higher frequency of PTEN alterations in bladder carcinoma (23%) tha n was previously recorded, with no accompanying mutations in the MX11 gene. (C) 2000 Wiley-Liss. Inc.