Deletions or point mutations in the p53 tumor-suppressor gene are currently the most commonly known genetic defects associated with human cancers. Loss of heterozygosity at 17p, the location of the p53 gene, has been estimated to be as high as 70%, whereas the frequency of point mutations in the highly-conserved exons 5, 6, 7 and 8 is approximately 25%. Li-Fraumeni syndrome consists of families with an inherited susceptibility for multiple cancers, the most common of which is breast cancer. All of the families examined thus far have an inherited p53 mutation. Breast cancer occurs in 8% of women during their lifetime; of these, it has been estimated that 31% are familial. A number of breast cancer families with tumors occurring in both male and female first-degree relatives have been examined. Of 32 families, six have so far been studied; three out of six have been found to be negative for p53 mutations (in exons 5, 6, 7 and 8), for loss of heterozygosity, and for overexpression of the p53 protein as analyzed by immunohistochemistry. Three patient DNA samples out of six have been found to have point mutations in the p53 gene. These inherited genetic defects in these breast cancer families appear to be different from the p53 mutations associated with the inherited breast cancer in the Li- Fraumeni family. Some of the patients in these families also had benign breast disease prior to development of malignant tumors. Currently, benign breast disease samples are being analyzed to investigate at what stage the p53 mutation occurred and whether p53 mutations can be used as a potential marker for diagnosis purposes. Several breast tumor cell lines have also been examined and it was found that two of the samples contained mutations in the p53 gene.
