Altered Expressions and Point Mutations of p53 in Human Bladder Transitional Cell Carcinomas

Kim, Bup Wan; Kwon, Tae Gyun; Noh, Ki Suck; Chung, Sung Kwang; Chang, Sae Kook; Chung, Woon Bok; Kim, Jung Wan

Abstract

The objective of this study was to characterise the pattern of p53 mutations in bladder tumor. In this study, 25 bladder transitional cell carcinomas were analyzed by immunohisochemistry (IHC) for p53 nuclear overexpression, and the results were compared with those of polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis in exon 5-8 of the p53 gene and DNA sequencing analysis. 15 out of 20 cases (75%) showed p53 nuclear immunoreactivities on IHC. On PCR-SSCP analysis, 10 out of 25 cases (40%) had abnormal shifts in mobility. 62% of the mutations were in exon 8. Direct DNA sequencing analysis were performed in these 10 cases to confirm the presence of mutated p53 genes and to determine the type of mutations. Sixteen point mutations were detected in 10 cases. Two specimens had double mutations and another two had triple mutations. G:C-->A:T transitions were the most frequent patterns (62.5%). One mutation was a premature stop codon and two were silent mutations. Three out of 10 had a point mutation at codon 285 (GAG/Glu-->AAG/Lys) and two had at codon 280 (AGA/Arg-->AAA/Lys). One of 16 mutations was transition at hot spot codon 273 with CpG site. These results suggest that altered expressions and point mutations of p53 occured in all grade of bladder cancer, but are more associated with high grade bladder tumors. To elucidate the carcinogenesis of bladder cancer, further studies should be carried out.