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Methylation of the BRCA1 promoter region in sporadic breast and ovarian cancer: correlation with disease characteristics

Abstract

Reduced expression of BRCA1 has been reported in sporadic breast cancer, although the mechanisms underlying this phenomenon remain unclear. Abnormal methylation leading to silencing of tumour suppressor genes has been implicated in tumorigenesis in a wide range of sporadic cancers. Therefore, we sought to determine the frequency of methylation within the BRCA1 promoter region in a large group of sporadic invasive breast (n=96) and ovarian (n=43) carcinomas using Southern analyses. Overall, methylation was detected in 11% of breast cancer cases and in 5% of ovarian tumours. Methylation of the BRCA1 promoter region was strongly correlated with lack of estrogen and progesterone receptor expression. It is clear from the frequency of abnormal methylation of the BRCA1 promoter region, that this cannot be the sole mechanism mediating the reduced expression of BRCA1 that has previously been reported to occur in the majority of invasive sporadic breast tumours. Nevertheless this study suggests that abnormal methylation of the BRCA1 promoter may be important in tumorigenesis in a subset of sporadic breast and ovarian cancers.

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Acknowledgements

AC was supported by the ICRF (Imperial Cancer Research Fund) and Generation Trust. We are grateful to Dr C Lewis for helping with the statistical analyses, to Dr I Fentiman for obtaining the tissue samples and to Dr D Grimwade, Dr M Brown and Dr D Barnes for critical reading of the manuscript.

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Catteau, A., Harris, W., Xu, CF. et al. Methylation of the BRCA1 promoter region in sporadic breast and ovarian cancer: correlation with disease characteristics. Oncogene 18, 1957–1965 (1999). https://doi.org/10.1038/sj.onc.1202509

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