Hypersensitive K303R oestrogen receptor-α variant not found in invasive carcinomas

Breast Cancer Research

D Ross Sibson¹  Helen Innes²  Penny A O'Neill²  Michael PA Davies¹ 

[1] Clatterbridge Cancer Research Trust, JK Douglas Laboratories, Clatterbridge Hospital, Bebington, Wirral, UK;Clatterbridge Centre for Oncology, Clatterbridge Hospital, Bebington, Wirral, UK

关键词: oestrogen receptor;    mutation;    hyperplasia;    carcinoma;    breast;   

Others  :  1115064
DOI  :  10.1186/bcr965

 received in 2004-02-02, accepted in 2004-10-18,  发布年份 2004

【 摘 要 】

Introduction

Genetic abnormalities or mutations in premalignant breast lesions may have a role in progression toward malignancy or influence the behaviour of subsequent disease. The A908G (Lys303→Arg) change in the gene encoding oestrogen receptor-α (ER-α) creates a hypersensitivity to oestradiol and would have significant consequences if present in breast carcinoma, especially those treated with endocrine therapy. We have therefore examined a panel of endocrine-treated invasive carcinomas for the presence of this mutation.

Methods

Sequencing of control DNA was shown to detect mutation present in as little as 15% of the starting material. Enrichment for the mutation by using MboII restriction digestion allowed the detection of mutant present at 1% or less. We applied these techniques to genomic DNA and cDNA from 136 invasive breast carcinomas.

Results

No evidence of the A908G mutation was found with either technique. The incidence of this mutation in our panel of tumours is therefore significantly less than previously reported.

Conclusion

The fact that the mutation was not found leads us to believe that this mutation is absent from most cells in invasive carcinomas and furthermore that the major expression product of the ER-α gene in cancers does not contain the K303R mutation. It is therefore unlikely to influence the effectiveness of endocrine treatment.

【 授权许可】

   
2004 Davies et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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