EXON-5 OF THE P53 GENE IS A TARGET FOR DELETIONS IN OVARIAN-CANCER

Missense point mutations, leading to inactivation of the p53 tumor sup pressor gene product, are currently the most frequent alterations in h uman cancer. Little, however, is known about small intragenic deletion s or insertions occurring in this locus of chromosome 17. We have anal yzed 56 primary ovarian tumors for the presence of such abnormalities. The analysis was based on multiplex PCR amplification of exons 1 thro ugh 11 of the p53 gene and fragment analysis of the generated PCR prod ucts. Mutations were detected in 14% (8 of 56) of the tumors. Deletion s were much more prevalent than insertions (seven vs one). Six of the deletions and the insertion affected exon 5, and the other deletion wa s in exon 7. Two deletions and the insertion did not disrupt the readi ng frame; the protein product was expressed in the tumor at high conce ntrations in all three cases. The other five deletions generated a fra meshift, which is predicted to result in the production of a truncated protein product. In the case of the deletions, a 2-5-bp repeat was pr esent close to the detected deletion, whereas the insertion duplicated the sequence immediately upstream of the insertion site. Overall our findings indicate that small intragenic p53 deletions/insertions are n ot rare events in ovarian cancer, and that p53 exon 5 is the target in the vast majority (88%) of the cases.