ANALYSES OF P53 GENE-MUTATIONS IN PRIMARY HUMAN BLADDER-CANCER

Mutations in the tumor suppressor gene p53 have been detected in many tumors. p53 gene mutations are also known to be involved in the progre ssion of human bladder cancers. We investigated structural alterations in the entire coding region of the p53 gene in primary human bladder cancers, using polymerase chain reaction and single-strand conformatio nal polymorphism analysis of RNA. Of 25 samples obtained from patients , 6 (24%) were found to have p53 alterations. DNA sequencing of the PC R products revealed 6 point mutations resulting in single amino-acid s ubstitutions in the regions of exons 5, 6, 7, 8, and 10 of this gene, respectively. Five of 6 cases with p53 mutations were invasive, with m etastasis or high-grade tumors. Interestingly, the one remaining case was a recurrent, low-grade, and superficial (pTa) tumor. In this early stage tumor, allelic loss of the p53 gene was also found, using a pol ymerase chain reaction-based restriction fragment length polymorphism assay. Our findings are in agreement with previous observations that p 53 mutations occurred in a high percentage of high grade or invasive b ladder cancers. Since mutation and allelic loss of the p53 gene were a lso detected in a low-grade and low-stage tumor in the present study, it is suggested that the p53 gene is involved in early stages of some bladder cancers as well as in their late stages.