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E-GEOD-69118 - DNA methylation of estrogen regulated enhancers defines endocrine sensitivity in breast cancer

Status
Released on 1 July 2015, last updated on 19 August 2015
Organism
Homo sapiens
Samples (8)
Array (1)
Protocols (6)
Description
Expression of estrogen receptor (ESR1) determines whether a breast cancer patient receives endocrine therapy as part of their adjuvant care, but does not guarantee patient response. However, the molecular factors that define endocrine response in ESR1-positive breast cancer patients remain poorly understood. Here, we characterize the DNA methylome of endocrine sensitivity and demonstrate the potential impact of differential DNA methylation on endocrine response in breast cancer. We show that DNA hypermethylation occurs predominantly at estrogen-responsive enhancers and is associated with reduced ESR1 binding and decreased gene expression of key regulators of ESR1-activity; thus providing a novel mechanism by which endocrine response is abated in ESR1-positive breast cancers. Conversely, we delineate that ESR1-responsive enhancer hypomethylation is critical in transition from normal mammary epithelial cells to endocrine responsive ESR1-positive cancer. Cumulatively these novel insights highlight the potential of ESR1-responsive enhancer methylation to both predict ESR1-positive disease and stratify ESR1-positive breast cancer patients as responders to endocrine therapy. Methylation profiling with Illumina's HumanMethylation450K array was performed on ESR1-positive hormone sensitive MCF7 cells, and three different well characterised endocrine resistant MCF7-derived cell lines; tamoxifen-resistant (TAMR), fulvestrant-resistant (FASR) and estrogen deprivation resistant (MCF7X) cells. For each cell line two biological replicates were profiled bringing the number of samples to eight.
Experiment type
methylation profiling by array 
Contacts
Elena Zotenko
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-69118.idf.txt
Sample and data relationshipE-GEOD-69118.sdrf.txt
Raw data (1)E-GEOD-69118.raw.1.zip
Processed data (1)E-GEOD-69118.processed.1.zip
Array designA-GEOD-13534.adf.txt
Links