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

  

Authors:	Archey, W. B.; McEachern, K. A.; Robson, M.; Offit, K.; Vaziri, S. A. J.; Casey, G.; Borg, A.; Arrick, B. A.
Article Title:	Increased CpG methylation of the estrogen receptor gene in BRCA1-linked estrogen receptor-negative breast cancers
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 < 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.
Keywords:	methylation; breast cancer; dna; tumors; estrogen receptor; transcriptional activation; brca1; mutations; expression; ovarian-cancer; promoter; carcinomas; sporadic breast
Journal Title:	Oncogene
Volume:	21
Issue:	46
ISSN:	0950-9232
Publisher:	Nature Publishing Group
Date Published:	2002-10-10
Start Page:	7034
End Page:	7041
Language:	English
ACCESSION:	WOS:000178424900006
DOI:	10.1038/sj.onc.1205844
PROVIDER:	wos
PUBMED:	12370825
Notes:	Article -- Source: Wos

https://synapse.mskcc.org/synapse/works/has_related_data_chk/69013