DNA methylation outliers in normal breast tissue identify field defects that are enriched in cancer

Andrew E Teschendorff (), Yang Gao, Allison Jones, Matthias Ruebner, Matthias W. Beckmann, David L. Wachter, Peter A. Fasching and Martin Widschwendter ()
Additional contact information
Andrew E Teschendorff: University College London
Yang Gao: CAS Key Lab of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences
Allison Jones: University College London
Matthias Ruebner: University Clinic Erlangen, Friedrich-Alexander University Erlangen-Nuremberg
Matthias W. Beckmann: University Clinic Erlangen, Friedrich-Alexander University Erlangen-Nuremberg
David L. Wachter: Institute of Pathology, University Clinic Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg
Peter A. Fasching: University Clinic Erlangen, Friedrich-Alexander University Erlangen-Nuremberg
Martin Widschwendter: University College London

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: Abstract Identifying molecular alterations in normal tissue adjacent to cancer is important for understanding cancer aetiology and designing preventive measures. Here we analyse the DNA methylome of 569 breast tissue samples, including 50 from cancer-free women and 84 from matched normal cancer pairs. We use statistical algorithms for dissecting intra- and inter-sample cellular heterogeneity and demonstrate that normal tissue adjacent to breast cancer is characterized by tens to thousands of epigenetic alterations. We show that their genomic distribution is non-random, being strongly enriched for binding sites of transcription factors specifying chromatin architecture. We validate the field defects in an independent cohort and demonstrate that over 30% of the alterations exhibit increased enrichment within matched cancer samples. Breast cancers highly enriched for epigenetic field defects, exhibit adverse clinical outcome. Our data support a model where clonal epigenetic reprogramming towards reduced differentiation in normal tissue is an important step in breast carcinogenesis.

Date: 2016
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms10478 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:7:y:2016:i:1:d:10.1038_ncomms10478

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

DOI: 10.1038/ncomms10478

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 ().