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Hypersensitive K303R oestrogen receptor-alpha variant not found in invasive carcinomas.

Davies MP, O'Neill PA, Innes H, Sibson DR - Breast Cancer Res. (2004)

Bottom Line: 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.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-alpha gene in cancers does not contain the K303R mutation.

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Affiliation: Clatterbridge Cancer Research Trust, JK Douglas Laboratories, Clatterbridge Hospital, Bebington, Wirral, UK. miked@ccrt.nhs.uk

ABSTRACT

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-alpha (ER-alpha) 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-alpha gene in cancers does not contain the K303R mutation. It is therefore unlikely to influence the effectiveness of endocrine treatment.

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Sample electrophoretograms of sequence data with and without enrichment by digestion with MboII. The sequence of the region of interest is shown: coding residues 903–913 (residues 1195–1205 of ESR1; GenBank accession number M12674). The position of the detected A908G mutation is marked with asterisks.
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Figure 1: Sample electrophoretograms of sequence data with and without enrichment by digestion with MboII. The sequence of the region of interest is shown: coding residues 903–913 (residues 1195–1205 of ESR1; GenBank accession number M12674). The position of the detected A908G mutation is marked with asterisks.

Mentions: PCR products were sequenced (Fig. 1) by using primers ERmut1 and ERmut2 and subjected to MboII digestion, reamplification and further sequencing as described below.


Hypersensitive K303R oestrogen receptor-alpha variant not found in invasive carcinomas.

Davies MP, O'Neill PA, Innes H, Sibson DR - Breast Cancer Res. (2004)

Sample electrophoretograms of sequence data with and without enrichment by digestion with MboII. The sequence of the region of interest is shown: coding residues 903–913 (residues 1195–1205 of ESR1; GenBank accession number M12674). The position of the detected A908G mutation is marked with asterisks.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1064111&req=5

Figure 1: Sample electrophoretograms of sequence data with and without enrichment by digestion with MboII. The sequence of the region of interest is shown: coding residues 903–913 (residues 1195–1205 of ESR1; GenBank accession number M12674). The position of the detected A908G mutation is marked with asterisks.
Mentions: PCR products were sequenced (Fig. 1) by using primers ERmut1 and ERmut2 and subjected to MboII digestion, reamplification and further sequencing as described below.

Bottom Line: 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.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-alpha gene in cancers does not contain the K303R mutation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Clatterbridge Cancer Research Trust, JK Douglas Laboratories, Clatterbridge Hospital, Bebington, Wirral, UK. miked@ccrt.nhs.uk

ABSTRACT

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-alpha (ER-alpha) 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-alpha gene in cancers does not contain the K303R mutation. It is therefore unlikely to influence the effectiveness of endocrine treatment.

Show MeSH
Related in: MedlinePlus