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Åke Borg

Åke Borg

Principal investigator

Åke Borg

Increased CpG methylation of the estrogen receptor gene in BRCA1-linked estrogen receptor-negative breast cancers

Author

  • WB Archey
  • KA McEachern
  • M Robson
  • K Offit
  • SAJ Vaziri
  • G Casey
  • Åke Borg
  • BA Arrick

Summary, in English

A distinctive feature of BRCA1-linked breast cancers is that they typically do not express estrogen receptor-alpha (ERalpha). Previous investigation suggests that methylation of CpGs within the ERa promoter mediates repression of gene expression in some ERalpha-negative breast cancers. To determine if methylation of CpGs within the ERalpha promoter is associated with BRCA1-linked breast cancers, we evaluated methylation in exon 1 of the ERalpha gene in 40 ERalpha-negative breast cancers, 20 of which were non BRCA1-linked and 20 BRCA1-linked. CpG methylation was evaluated by either methylation-sensitive restriction digest (HpaII), methylation-sensitive PCR (MSP), or direct sequencing of bisulfite-treated genomic DNA. Results from HpaII digests and MSP documented a high degree of methylation, the MSP data showing slightly higher methylation in the BRCA1-linked group. CpGs analysed by direct sequencing showed an overall average methylation of 25% among non BRCA1-linked cancers and 40% among BRCA1-linked cancers (P=0.0031). The most notable difference was found at five particular CpGs, each of which exhibited a greater than twofold increase in methylation in the BRCA1-linked group compared to the non BRCA1-linked group (P < 0.03 for each CpG). Methylation of certain critical CpGs may represent an important factor in transcriptional repression of the ERa gene in BRCA1-linked breast cancers.

Department/s

  • Breastcancer-genetics

Publishing year

2002

Language

English

Pages

7034-7041

Publication/Series

Oncogene

Volume

21

Issue

46

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cancer and Oncology

Keywords

  • methylation
  • BRCA1
  • breast cancer
  • estrogen receptor

Status

Published

ISBN/ISSN/Other

  • ISSN: 1476-5594