High incidence of mutations of the p53 gene detected in ovarian tumours by the use of chemical mismatch cleavage.

We have investigated a series of ovarian tumours for evidence of mutations in the p53 tumour suppressor gene. In this study we have made use of the chemical mismatch cleavage technique which, from analyses of other genes, has been shown to consistently identify all point mutations present within a region of DNA. This approach revealed mutations of p53 in 11/20 tumours studied, mainly in exons 5 or 7. After sequencing the relevant regions of the gene it was shown that ten of these mutations would have resulted in an amino acid substitution in the protein and only one represented a polymorphism. The observed incidence of p53 missense mutations in our series (50%) was the highest recorded in ovarian tumours and demonstrated the potential of the mismatch cleavage technique as a reliable method for the detection of p53 mutations in human tumours.