P53 mutations appear an acquired rather than an inherited event in sporadic ovarian cancer: a study of DNA from tumor specimens and blood leukocytes

Abstract

The p53 gene is located on the small arm of chromosome 17 and mutations or hyperexpression are found in a high percentage of ovarian cancer cases (44–92%). We studied DNA extracted from blood leukocytes of 38 ovarian cancer patients; tumor tissues were also available for analysis in 20 of these cases. Specimens were examined using Single Strand Conformation Polymorphism (SSCP) analysis and direct genomic sequencing of the p53 gene. Exons from 2 to 11 were studied in blood and tumoral tissues. Single Strand Conformation Polymorphism analysis and direct genomic sequencing showed that seven patients (18.4%) had a germline alteration of the p53 gene, but only two of them (5.2%) led to an amino acid change. The other five patients had only a silent mutation which does not change the amino acid (two patients) or had intronic mutations (four patients) whose interpretation is uncertain. Somatic mutations of the p53 gene were found in nine of the 20 tumoral tissues (45%). One tumor contained two mutations in the p53 gene (no. 9). Our study, though preliminary and based on a small group of patients, suggests that classic p53 mutations in sporadic ovarian cancer cases are common, but they are not generally found in the germinal line.