Aberration of the p53 gene in human pancreatic ductal adenocarcinomas

Abstract

The p53 gene is considered one of the tumor suppressor genes which negatively regulate cell growth and division in the wild type, and its mutations in evolutionary conserved exons are common in diverse types of human malignancies(l). Pancreatic ductal adenocarcinoma is well known as a tumor carrying activated Ki-ras gene(2), but other genes that correlate to multistep carcinogenesis are not yet known. Therefore, we analyzed aberrations of exons 5 to 8 of the p53 gene in 8 cases of advanced pancreatic ductal adenocarcinomas by PCR-SSCP analysis. The method of PCR-SSCP analysis of the p53 gene was described previously by Murakami et al.(3). Genomic DNA were extracted from fresh surgical specimens and, as a noncancerous control tissue the lymphocytes of the same patients were used. The PCR products which were labeled with e_np dCTP were applied to 5% polyacrylamide gel containing 10% glycerol and, after electrophoresis, the gel was dried and subjected to autoradiography. As shown in Figure, mobility shifts which indicate structural abnormalities were observed in 3 of 8 cases, 2 cases in exon 5 and 1 case in exon 6, respectively. No extra-band was seen in noncancerous tissue of the same patients. These results suggest the involvement of the p53 gene aberration in human pancreatic ductal carcinogenesis.