P53 MUTATION IS A COMMON GENETIC EVENT IN OVARIAN-CARCINOMA

Using the single-strand conformational polymorphism technique, we have screened 66 malignant ovarian tumors for p53 mutation in exons 5 to 8 . Thirty-four of the tumors demonstrated a single-strand conformationa l polymorphism band shift in this region of the gene, including 6 in e xon 5, 7 in exon 6, 12 in exon 7, and 10 in exon 8 (one of the tumors showed a shift for exons 7 and 8). All of the single-strand conformati onal polymorphism shifts have been further characterized by DNA sequen cing, and 31 of 35 have been shown to represent genuine DNA alteration s. These include 27 point mutations (23 missense, 2 nonsense, and 2 si lent mutations), 3 deletions (a 2-base pair deletion introducing, by f rameshift, a stop codon further downstream; a 3-base pair deletion; an d an unusual 6-base pair deletion made up of separate 2-base pair and 4-base pair deletions), and a 4-base pair insertion (introducing a sto p codon downstream). In total, 29 of the 66 (44%) carcinomas analyzed had mutations affecting the primary sequence of the p53 protein. p53 m utation was found in tumors of all International Federation of Gynecol ogists and Obstetricians stages, suggesting that it might be an earlie r genetic event in the progression of epithelial ovarian tumors than p reviously thought. A significantly greater number of p53 mutations wer e seen in high-grade serous carcinomas than in those of endometrioid a nd mucinous types (0.02 > P > 0.01). Analysis of the distribution of p oint mutations showed no preference for any particular mutation type.