A POINT MUTATION IN THE PUTATIVE TATA BOX, DETECTED IN NONDISEASED INDIVIDUALS AND PATIENTS WITH HEREDITARY BREAST-CANCER, DECREASES PROMOTER ACTIVITY OF THE 17-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1 GENE-2 (EDH17B2) IN-VITRO

EDH17B2, the gene encoding 17 beta-hydroxysteroid dehydrogenase type 1 , has been suggested as a candidate for the familial breast cancer gen e, BRCA1, located on 17q12-q21. We analyzed the promoter region of EDH 17B2 in DNA from 20 control individuals and 40 patients with familial breast cancer. Two frequent (designated vI and vIII) and two rare (vII and vIV) nucleotide variations were present in both the breast cancer patients and the controls, except the alteration vII, which was found only in one patient. Although the data do not support the identificat ion of EDH17B2 as the BRCA1 gene, it is of interest that point mutatio n vIV (A --> C) was located in the putative TATA box of the EDH17B2 ge ne. Reporter gene analyses showed that the mutation vIV decreases EDH1 7B2 promoter activity by an average of 45% in in vitro assays, suggest ing that nucleotide A at position -27 is significant for efficient tra nscription. (C) 1994 Academic Press, Inc.