The molecular genetic events of ovarian cancer
The current study has shown by SSCP analysis and direct sequencing that almost 45% of such tumours contain mutations in the p53 tumour suppressor gene. The observed mutational spectrum is consistent mainly with a spontaneous mechanism for ovarian tumourigenesis. A slight excess of A:T > T:A transversions, however, which is not observed generally in ovarian tumours, suggests that ovarian cancer development in Scotland may be partially attributable to an exogenous factor which is not involved substantially in the aetiology of the disease elsewhere. The potential relationship between p53 aberration and patient survival was investigated. Although p53 aberration was not found to be an independent prognostic indicator, it was associated with early disease recurrence and increased patient mortality. Only advanced tumour stage was found to be independently associated with decreased patient survival. A significant association, however, was observed between p53 aberrations and advanced tumour stage. In an attempt to identify other regions involved in the aetiology of ovarian cancer, sporadic ovarian carcinomas were investigated for allele loss on chromosome 17q. Deletion of all or part of chromosome 17q was frequently observed, with 79% of tumours exhibiting allele loss at one or more of the loci studied. Two common regions of deletion (CRD) were identified: CRD1 is defined by the region of chromosome 17q proximal to D17S579 at 17q21; CRD2 includes the region distal to D17S74. These findings suggest that a gene, potentially a tumour suppressor gene, located in each of these regions is frequently deleted in ovarian tumours.