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

Archey, WB ; McEachern, KA ; Robson, M ; Offit, K ; Vaziri, SAJ ; Casey, G ; Borg, Åke LU and Arrick, BA (2002) In Oncogene 21(46). p.7034-7041
Abstract
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... (More)
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. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
methylation, BRCA1, breast cancer, estrogen receptor
in
Oncogene
volume
21
issue
46
pages
7034 - 7041
publisher
Nature Publishing Group
external identifiers
  • wos:000178424900006
  • pmid:12370825
  • scopus:0037057324
  • pmid:12370825
ISSN
1476-5594
DOI
10.1038/sj.onc.1205844
language
English
LU publication?
yes
id
5b8cc249-4359-431e-8fe0-464f03ef09b1 (old id 325952)
date added to LUP
2016-04-01 11:42:02
date last changed
2022-01-26 08:56:04
@article{5b8cc249-4359-431e-8fe0-464f03ef09b1,
  abstract     = {{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 &lt; 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.}},
  author       = {{Archey, WB and McEachern, KA and Robson, M and Offit, K and Vaziri, SAJ and Casey, G and Borg, Åke and Arrick, BA}},
  issn         = {{1476-5594}},
  keywords     = {{methylation; BRCA1; breast cancer; estrogen receptor}},
  language     = {{eng}},
  number       = {{46}},
  pages        = {{7034--7041}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Oncogene}},
  title        = {{Increased CpG methylation of the estrogen receptor gene in BRCA1-linked estrogen receptor-negative breast cancers}},
  url          = {{http://dx.doi.org/10.1038/sj.onc.1205844}},
  doi          = {{10.1038/sj.onc.1205844}},
  volume       = {{21}},
  year         = {{2002}},
}