A STUDY OF p53 GENE MUTATIONS IN FAMILIAL, SPORADIC, AND MALE BREAST CANCER

Abstract

Mutations of the p53 tumor suppressor gene are the most common genetic lesion in human cancers; p53 mutations have also been reported in familial breast cancer, as in Li-Fraumeni syndrome (LFS). In this study, the frequencies and types of the p53 mutations in breast cancer tissues were investigated. Tissue samples of benign breast disease (BBD) from women who later developed both familial (n=6) and sporadic (n=10) breast cancer were examined. Among the cases with a family history of breast cancer and BBD, a third of the tumor samples had p53 gene mutations. The p53 gene was also analyzed in matched, archival BBD lesions; however, no mutations were observed (0 out of 2). These results suggest that the p53 mutations occur during advanced stages of tumor progression. In sporadic breast cancer cases with a history of BBD, p53 point mutations were observed in four samples (4 out of 10); p53 gene mutations were not found in the breast tumor tissues of 10 additional women with a family history of breast cancer, but no previous BBD. Family history of breast cancer does not appear to affect the frequency of p53 mutations in women with a previous history of BBD. This study also investigated the mutational spectra of the p53 gene in the much rarer male breast cancer. Of 10 samples analyzed for p53 mutations in exons 5, 6, 7 and 8, only two showed point mutations corresponding to amino acid residues 248 and 290. One of the point mutations turned out to be a silent change, thus representing only a DNA polymorphism. The number of p53 mutations in male breast cancer (10%), unlike females (30%), does not appear to be as frequent.