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Androgen receptor gene mutation in male breast cancer.
- Source :
-
Human molecular genetics [Hum Mol Genet] 1993 Nov; Vol. 2 (11), pp. 1799-802. - Publication Year :
- 1993
-
Abstract
- We screened thirteen male breast cancers for the presence of germline mutations in exons 2 and 3 encoding the DNA-binding domain of the androgen receptor. These two exons were amplified from genomic DNA extracted from patients' white blood cells. In one of these thirteen patients, single strand conformation polymorphism and direct sequencing detected a guanine-adenine point mutation at nucleotide 2185 that changes Arg608 into Lys in a highly conserved region of the second zinc finger of the androgen receptor. This mutation occurred in a 38 year old man with partial androgen insensitivity syndrome and normal androgen-binding capacity in cultured genital skin fibroblasts. To our knowledge, only one germline Arg to Gln androgen receptor gene mutation has been previously reported at position 607 in male breast cancer. This androgen receptor mutation along with the Arg608 into Lys mutation we describe, suggests that this genetic abnormality is not fortuitous: a decrease in androgen action within the breast cells could account for the development of male breast cancer by the loss of a protective effect of androgens on these cells. Activation of estrogen regulated genes by the change of DNA-binding characteristics of the mutant androgen receptor cannot, however, be ruled out.
- Subjects :
- Adult
Amino Acid Sequence
Base Sequence
DNA blood
DNA isolation & purification
DNA Primers
Exons
Female
Humans
Leukocytes metabolism
Male
Molecular Sequence Data
Pedigree
Polymerase Chain Reaction
Polymorphism, Genetic
Skin metabolism
Breast Neoplasms genetics
DNA-Binding Proteins genetics
Men
Point Mutation
Receptors, Androgen genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0964-6906
- Volume :
- 2
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Human molecular genetics
- Publication Type :
- Academic Journal
- Accession number :
- 8281139
- Full Text :
- https://doi.org/10.1093/hmg/2.11.1799