p53 gene mutations in gastric cancer metastases and in gastric cancer cell lines derived from metastases

Abstract

Structural alterations of the p53 gene were investigated in tissue specimens of gastric and cervical cancers and in cell lines of gastric, esophageal, and cervical cancers, by polymerase chain reaction-single-strand conformation polymorphism analysis. Two of the four gastric cancer metastases and four of the eight cell lines originally established from gastric cancer metastases were found to have p53 gene alterations in the exon 5 to 11 region; point mutations and amino acid replacements were detected in a liver and an ovary metastasis at exon 7, in the TMK1 and MKN1 cell lines at exon 5, and in the OKAJIMA cell line at exon 10. The normal allele was not found in these cell lines. In the KATO-III cell line, gross deletion and rearrangement of the p53 gene were noted. However, no p53 mutations were identified in 19 primary lesions of gastric cancer, suggesting that the p53 gene abnormality preferentially occurs in the advanced stages of gastric cancer. In contrast to the gastric cancer, none of the 13 esophageal cancer cell lines, including two cell lines established from metastases, and none of the four cervical cancer cell lines showed any aberration in exons 5 to 11 of the p53 gene. During the course of the study, a novel polymorphism in intron 7 of the p53 gene was found, which can be recognized by restriction enzyme digestions of the polymerase chain reaction product.