DNA methylation outliers in normal breast tissue identify field defects that are enriched in cancer
Citations Over TimeTop 1% of 2016 papers
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.
Related Papers
- → Biophysical regulation of cell reprogramming(2017)34 cited
- → Direct reprogramming 101(2010)20 cited
- → Advances in Reprogramming to Pluripotency(2015)8 cited
- → Cellular Reprogramming: Current Technology, Perspectives, and Generation of Induced Pluripotent Cells(2010)
- Progresses on Mechanisms on Reprogramming of Somatic Cells in Mammals(2013)