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

Andrew Stone1, Elena Zotenko1, Warwick J Locke1

  • 11] Epigenetics Research Program, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia [2] Faculty of Medicine, St Vincent's Clinical School, UNSW, NSW 2052 &St Vincent's Hospital, Sydney, New South Wales 2010, Australia.

Nature Communications
|July 15, 2015
PubMed

Insights

DNA methylation patterns in oestrogen receptor-positive breast cancer influence endocrine therapy response. Methylation changes at oestrogen-responsive enhancers can predict treatment outcomes and stratify patients for endocrine therapy.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Oestrogen receptor (ESR1) status guides endocrine therapy for breast cancer, but response is variable.
  • Molecular determinants of endocrine response in ESR1-positive breast cancer are not fully understood.

Purpose of the Study:

  • To investigate the role of DNA methylation in endocrine sensitivity in breast cancer.
  • To identify methylation patterns associated with endocrine therapy response.

Main Methods:

  • DNA methylome characterization of endocrine-sensitive breast cancer.
  • Analysis of DNA methylation at oestrogen-responsive enhancers.
  • Assessment of ESR1 binding and gene expression.

Main Results:

  • DNA hypermethylation at oestrogen-responsive enhancers correlates with reduced ESR1 binding and gene expression, impairing endocrine response.
  • ESR1-responsive enhancer hypomethylation is crucial for the transition to endocrine-responsive cancer.
  • Differential DNA methylation impacts endocrine response in ESR1-positive breast cancers.

Conclusions:

  • ESR1-responsive enhancer methylation is a key epigenetic mechanism affecting endocrine therapy response.
  • DNA methylation patterns can potentially predict ESR1-positive breast cancer and stratify patients for endocrine therapy.

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