p53 mutations in urinary bladder cancer

We have screened for mutations in exons 5-8 of the p53 gene in a series con sisting of 189 patients with urinary bladder neoplasms. 82 (44%) neoplasms were lowly malignant (Ta, G1-G2a) and 106 (56%) were highly malignant (G2b- G4 or greater than or equal to T1). Only one mutation was in a lowly malign ant urinary bladder neoplasm, in total we found p53 mutations in 26 (14%) o f the 189 patients. 30% of the samples had loss of heterozygosity (LOH) for one or both of the p53 exogenic (CA)n repeat and the p53 intragenic (AAAAT )n repeat markers. 31 samples (21%) showed LOH but were not mutated, sugges ting other mechanisms inactivating p53 than mutations. 4 mutations were fou nd at codon 280 and 2 mutations were found at codon 285, 2 previously repor ted hot spots for urinary bladder cancer. The study indicate a boundary bet ween G2a and G2b tumours concerning the occurrence of genetic events affect ing p53 function, moderately differentiated (G2) urinary bladder neoplasms probably are genetically heterogeneous which supports the suggestion that t hey should not be grouped together but instead, for example, be categorized as either lowly or highly malignant. (C) 2001 Cancer Research Campaign.