FREQUENT DETECTION OF MUTATIONS IN THE 5'-FLANKING REGION OF THE PROSTATE-SPECIFIC ANTIGEN GENE IN FEMALE BREAST-CANCER

Prostate-specific antigen (PSA) is expressed in normal, hyperplastic a nd cancerous female breast tissue. Expression is regulated by steroid hormones. Some breast tumours produce very high levels of PSA, while o thers do not express any PSA. In this study, we selected three primary breast tumours which overexpressed PSA (PSA protein concentration in tumour cytosols >4300 ng/l) and three tumours which were negative for PSA (<1 ng/l). We extracted DNA and sequenced all five exons of the PS A gene. No mutations were found in the PSA coding sequence in any of t he tumours. We identified only two polymorphic sites in exon 2. We als o sequenced parts of the 5' flanking region of the PSA gene in five tu mours. All tumour DNAs contained abnormalities which consisted of poin t mutations and deletions of 1-7 base pairs. Except for one tumour whi ch had only a 3 base pair deletion, all other tumours had multiple abn ormalities (up to seven in one tumour). The deletions occurred adjacen t to direct repeats similarly to deletions seen in the p53 gene. Our d ata suggest that the coding sequence of PSA is not mutated in breast c ancer. However, the 1.4 kb 5'-flanking region was mutated in all five tumours tested. The importance of this observation in relation to PSA gene regulation and breast cancer pathobiology remain to be determined . (C) 1997 Elsevier Science Ltd.