Advanced

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)
Please use this url to cite or link to this publication:
author
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
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
2007-08-07 15:41:17
date last changed
2017-03-19 03:24:40
@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},
  keyword      = {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},
  volume       = {21},
  year         = {2002},
}