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

Teschendorff AE, Gao Y, Jones A, Rübner M, Beckmann M, Wachter D, Fasching P, Widschwendter M (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 7

Pages Range: 10478

DOI: 10.1038/ncomms10478

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.

Authors with CRIS profile

Matthias Rübner Department of Obstetrics and Gynaecology Matthias Beckmann Lehrstuhl für Geburtshilfe und Frauenheilkunde David Wachter Institute of Pathology Peter Fasching Professur für Translationale Frauenheilkunde und Geburtshilfe

Involved external institutions

University College London (UCL) GB United Kingdom (GB) Chinese Academy of Sciences (CAS) / 中国科学院 CN China (CN)

How to cite

APA:

Teschendorff, A.E., Gao, Y., Jones, A., Rübner, M., Beckmann, M., Wachter, D.,... Widschwendter, M. (2016). DNA methylation outliers in normal breast tissue identify field defects that are enriched in cancer. Nature Communications, 7, 10478. https://doi.org/10.1038/ncomms10478

MLA:

Teschendorff, Andrew E., et al. "DNA methylation outliers in normal breast tissue identify field defects that are enriched in cancer." Nature Communications 7 (2016): 10478.

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