Mutations of p53 gene in gastric carcinoma in Taiwan.

ABSTRACT

BACKGROUND: p53 gene mutation and p53 protein accumulation is the most common event in human cancers. The present study was conducted to investigate the occurrence of p53 mutations in patients with gastric carcinoma in Taiwan. MATERIALS AND METHODS: Tumor samples from 36 patients with primary gastric carcinoma undergoing radical gastrectomy were evaluated. The mutational status of the p53 (exons 5 to 8) was screened by polymerase chain reaction/single strand conformation polymorphism (PCR-SSCP) analysis followed by direct sequencing. These results were compared with p53 protein expression as assessed by immunohistochemical staining. RESULTS: Of all 36 gastric carcinomas, mutations of the p53 gene were found in 7 cases (19.4%). These results from direct sequencing indicated that mutations consisted of five missence mutations, one silent mutation and one mutation within the splice donor site of intron 5. Mutations were found at codon 145 in exon 5 (1 case), intron 5 (1 case), codon 248 in exon 7 (1 case), codon 251 in exon 7 (2 cases), codon 285 in exon 8 (1 case) and codon 287 in exon 8 (1 case). The mutation hot spot at codon 251 in gastric cancer has not been observed previously. Over-expression of p53 oncoprotein was observed in 10 patients (27.8%) immunohistochemically. CONCLUSIONS: p53 gene mutation might contribute to the pathogenesis of human gastric carcinoma. However, the suggestion awaits further investigation for confirmation.