Screening for ESR mutations in breast and ovarian cancer patients

In the present study, leukocyte DNA from 143 patients with familial clustering of breast and/or ovarian cancer and tumour DNA from 96 breast carcinomas were screened for base mutations in the estrogen receptor gene (ESR). Three patients with a family history of cancer were carrying a Gly160Cys germline substitution. This alteration was also detected in eight (four females and four males) of 729 controls (366 female, 363 males), indicating that the substitution probably represents a polymorphism. However, in the 229 female controls in whom family history of cancer was known, one of two who had a sister with breast cancer was carrying the variant allele. Hence, a possible clinical significance of the glycine into cysteine cannot be completely ruled out and should be further investigated. Somatic mutations were not detected in any of the tumours studied, and the present data do not provide support for somatic ESR base mutations as an important mechanism for hormonal therapy resistance in estrogen receptor‐positive breast carcinomas. Hum. Mutat. 9:531–536, 1997. © 1997 Wiley‐Liss, Inc.

[1]  A. Børresen.  Constant Denaturant Gel Electrophoresis (CDGE) in Mutation Screening , 1996 .

[2]  D. Bentley,et al.  Identification of the breast cancer susceptibility gene BRCA2 , 1995, Nature.

[3]  A. Børresen,et al.  Alterations of the TP53 gene as a potential prognostic marker in breast carcinomas. Advantages of using constant denaturant gel electrophoresis in mutation detection. , 1995, Diagnostic molecular pathology : the American journal of surgical pathology, part B.

[4]  S. Fuqua,et al.  Coexpression of wild-type and variant oestrogen receptor mRNAs in a panel of human breast cancer cell lines. , 1995, British Journal of Cancer.

[5]  M. Sluyser.  Mutations in the estrogen receptor gene , 1995, Human mutation.

[6]  Steven E. Bayer,et al.  A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. , 1994, Science.

[7]  G. T. Budd,et al.  Estrogen receptor mutations in tamoxifen-resistant breast cancer. , 1994, Cancer research.

[8]  J. Boyle,et al.  Localization of the estrogen receptor locus (ESR) to chromosome 6q25.1 by FISH and a simple post-FISH banding technique. , 1993, Genomics.

[9]  D. Easton,et al.  Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium. , 1993, American journal of human genetics.

[10]  R. Eeles,et al.  Detection of point mutations in the p53 gene: Comparison of single‐strand conformation polymorphism, constant denaturant gel electrophoresis, and hydroxylamine and osmium tetroxide techniques , 1993, Human mutation.

[11]  S. Lehrer,et al.  Oestrogen and progesterone receptor dissociation and family history of breast cancer , 1992, The Lancet.

[12]  C. Benz,et al.  Truncated forms of DNA-binding estrogen receptors in human breast cancer. , 1991, The Journal of clinical investigation.

[13]  M. King,et al.  Possible linkage of the estrogen receptor gene to breast cancer in a family with late-onset disease. , 1991, American journal of human genetics.

[14]  M. Sluyser,et al.  Steroid/thyroid receptor-like proteins with oncogenic potential: a review. , 1990, Cancer research.

[15]  P. Chambon,et al.  The contribution of the N- and C-terminal regions of steroid receptors to activation of transcription is both receptor and cell-specific. , 1989, Nucleic acids research.

[16]  P. Chambon,et al.  Genomic organization of the human oestrogen receptor gene. , 1988, The EMBO journal.

[17]  R. Evans,et al.  The steroid and thyroid hormone receptor superfamily. , 1988, Science.