P53 GENE-MUTATIONS IN WOMEN WITH BREAST-CANCER AND A PREVIOUS HISTORYOF BENIGN BREAST DISEASE

Mutations of the p53 tumour suppressor gene are the most common geneti c lesions in human cancers and have been reported in breast cancer as part of the Li-Fraumeni syndrome. In the present study, we determined frequencies and types of the p53 mutations in breast cancer tissues in women with a history of benign breast disease (BBD) identified in Flo rence, Italy, with (n = 6) or without (n = 10) a family history of bre ast cancer. Among the cases with a family history of breast cancer and BBD, 2 out of 6 had p53 gene mutations in cancer samples. 1 patient h ad a mutation at codon 248 and the other had double mutations at codon s 243 and 241. In these cases, the p53 gene was also analysed in the t issue samples from previous BBD lesions; however, no mutations were ob served (0 out of 6). These results suggest that the p53 mutations occu r during advanced stages of tumour progression. In sporadic breast can cer cases with a history of BBD, p53 point mutations were observed in four samples (4 out of 10). Two of these mutations turned out to be si lent changes and one of the samples showed triple mutations at amino a cid positions 267, 277 and 296. No p53 gene mutations were found in th e breast tumour tissues of 10 additional women from the same area with a family history of breast cancer, but no previous BBD (0 out of 10). Family history of breast cancer does not appear to affect the frequen cy of p53 mutations in women with a previous history of BBD.