Åke Borg
Principal investigator
Increased CpG methylation of the estrogen receptor gene in BRCA1-linked estrogen receptor-negative breast cancers
Author
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