DNA methylation of oestrogen-regulated enhancers defines endocrine sensitivity in breast cancer

Andrew Stone, Elena Zotenko, Warwick J. Locke, Darren Korbie, Ewan K. A. Millar, Ruth Pidsley, Clare Stirzaker, Peter Graham, Matt Trau, Elizabeth A. Musgrove, Robert I. Nicholson, Julia M. W. Gee and Susan J. Clark ()
Additional contact information
Andrew Stone: Epigenetics Research Program, Garvan Institute of Medical Research
Elena Zotenko: Epigenetics Research Program, Garvan Institute of Medical Research
Warwick J. Locke: Epigenetics Research Program, Garvan Institute of Medical Research
Darren Korbie: Australian Institute for Bioengineering and Nanotechnology, University of Queensland
Ewan K. A. Millar: Translational Breast Cancer Research, The Kinghorn Cancer Centre, Garvan Institute of Medical Research
Ruth Pidsley: Epigenetics Research Program, Garvan Institute of Medical Research
Clare Stirzaker: Epigenetics Research Program, Garvan Institute of Medical Research
Peter Graham: Faculty of Medicine, UNSW
Matt Trau: Australian Institute for Bioengineering and Nanotechnology, University of Queensland
Elizabeth A. Musgrove: Faculty of Medicine, St Vincent’s Clinical School, UNSW, NSW 2052 & St Vincent’s Hospital
Robert I. Nicholson: Breast Cancer Molecular Pharmacology Group, School of Pharmacy and Pharmaceutical Sciences, Cardiff University
Julia M. W. Gee: Breast Cancer Molecular Pharmacology Group, School of Pharmacy and Pharmaceutical Sciences, Cardiff University
Susan J. Clark: Epigenetics Research Program, Garvan Institute of Medical Research

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: Abstract Expression of oestrogen receptor (ESR1) determines whether a breast cancer patient receives endocrine therapy, but does not guarantee patient response. 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 oestrogen-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.

Date: 2015
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms8758 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8758

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms8758

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().