ABERRATIONS OF THE P53 TUMOR-SUPPRESSOR GENE IN HUMAN EPITHELIAL OVARIAN-CARCINOMA

Aberrations of the p53 gene in 26 surgical specimens of human epitheli al ovarian carcinomas were examined by single-strand conformation poly morphism (SSCP) analysis of polymerase chain reaction (PCR) products. Seven (27%) of the tumors demonstrated a SSCP band shift in exons 4 to 9 of the gene, including 5 in the region encompassing exons 5 and 6, 1 in exon 7, and 1 in the region encompassing exons 8 and 9. Mutations were clustered in exon 5 in highly conserved regions of the p53 gene. All of the abnormal DNA fragments have been further characterized by direct DNA sequencing. These include five missense mutations (five tra nsitions), a one-base-pair deletion introducing, by frameshift, a stop codon further downstream, and a two-base-pair insertion introducing a stop codon downstream by frameshift. Most mutations were base substit utions, and were clustered in exon 5 (71%), especially codons 175 and 179. The aberrations of the p53 gene were only found in tumors of FIGO stages III and IV. Histologic grading was also reviewed with respect to p53 aberrations. The aberrations were absent in well-differentiated carcinomas. The more undifferentiated the primary tumor, the more fre quent p53 mutation (P < 0.05). Our results indicated that the aberrati ons of the p53 gene were common in epithelial ovarian cancers and p53 aberration may occur late during ovarian cancer evolution. (C) 1995 Ac ademic Press, Inc.