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

Genomics. 1994 Sep 1;23(1):250-2. doi: 10.1006/geno.1994.1487.

Abstract

EDH17B2, the gene encoding 17 beta-hydroxysteroid dehydrogenase type 1, has been suggested as a candidate for the familial breast cancer gene, BRCA1, located on 17q12-q21. We analyzed the promoter region of EDH17B2 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 identification of EDH17B2 as the BRCA1 gene, it is of interest that point mutation vIV (A-->C) was located in the putative TATA box of the EDH17B2 gene. Reporter gene analyses showed that the mutation vIV decreases EDH17B2 promoter activity by an average of 45% in in vitro assays, suggesting that nucleotide A at position -27 is significant for efficient transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 17-Hydroxysteroid Dehydrogenases / classification
  • 17-Hydroxysteroid Dehydrogenases / genetics*
  • BRCA1 Protein
  • Base Sequence
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / genetics*
  • Chromosomes, Human, Pair 17*
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics
  • Genes
  • Genes, Reporter
  • Genetic Linkage
  • Genetic Testing
  • Humans
  • Isoenzymes / genetics*
  • Molecular Sequence Data
  • Neoplasm Proteins*
  • Neoplastic Syndromes, Hereditary / genetics*
  • Point Mutation*
  • Polymorphism, Single-Stranded Conformational
  • TATA Box*
  • Transcription Factors*
  • Transcription, Genetic

Substances

  • BRCA1 Protein
  • DNA, Neoplasm
  • Isoenzymes
  • Neoplasm Proteins
  • Transcription Factors
  • 17-Hydroxysteroid Dehydrogenases