HUMAN FAMILIAL AND SPORADIC BREAST-CANCER - ANALYSIS OF THE CODING REGIONS OF THE 17-BETA-HYDROXYSTEROID DEHYDROGENASE 2 GENE (EDH17B2) USING A SINGLE-STRAND CONFORMATION POLYMORPHISM ASSAY
A. Mannermaa et al., HUMAN FAMILIAL AND SPORADIC BREAST-CANCER - ANALYSIS OF THE CODING REGIONS OF THE 17-BETA-HYDROXYSTEROID DEHYDROGENASE 2 GENE (EDH17B2) USING A SINGLE-STRAND CONFORMATION POLYMORPHISM ASSAY, Human genetics, 93(3), 1994, pp. 319-324
17 beta-Hydroxysteroid dehydrogenase (17HSD) is one of;the key enzymes
in estrogen metabolism, catalyzing the reversible reaction between es
tradiol and the less active estrogen, estrone. The gene encoding this
enzyme, EDH17B2, has been mapped to chromosome 17, region q12-q21, in
the vicinity of BRCA1, an as yet unidentified gene that appears to be
involved in familial breast cancer and in familial ovarian cancer. The
possibility that EDH17B2 gene is the same as BRCA1 was tested by scre
ening for mutations in the coding regions of EDH17B2, using a polymera
se chain reaction/single-strand conformation polymorphism method. An A
-->G transition creating a new BstUI site at exon 6 was the only frequ
ent sequence alteration found in the coding region of the gene. This m
utation also led to an amino acid substitution of serine to glycine at
position 312 (312(S)-->312(G)) in the 17HSD protein. Since the nucleo
tide change was detected both in specimens from patients with familial
or sporadic cancer and in control samples, and at similar rates, this
mutation appears to be of a polymorphic nature. In addition, a rare p
olymorphism located at intron 5 was detected. This C-->T substitution
creates a BbvI site and is not thought to have any effect on 17HSD act
ivity. The results indicate that there are no major alterations in the
coding areas of EDH17B2 and thus studies testing the hypothesis that
EDH17B2 may be the same as BRCA1 should be extended to the promoter an
d regulatory elements of EDH17B2.