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论文题目: DNA methylation outliers in normal breast tissue identify field defects that are enriched in cancer
英文论文题目: DNA methylation outliers in normal breast tissue identify field defects that are enriched in cancer
第一作者: Teschendorff, AE; Gao, Y; Jones, A; Ruebner, M; Beckmann, MW; Wachter, DL; Fasching, PA; Widschwendter, M
英文第一作者: Teschendorff, AE; Gao, Y; Jones, A; Ruebner, M; Beckmann, MW; Wachter, DL; Fasching, PA; Widschwendter, M
联系作者: AE (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, CAS Key Lab Computat Biol, Shanghai 200031, Peoples R China.
英文联系作者: AE (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, CAS Key Lab Computat Biol, Shanghai 200031, Peoples R China.
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发表年度: 2016
卷: 7
期:
页码: 10478
摘要: 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.
英文摘要: 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.
刊物名称: NATURE COMMUNICATIONS
英文刊物名称: NATURE COMMUNICATIONS
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学科: Multidisciplinary Sciences
英文学科: Multidisciplinary Sciences
影响因子: 12.124
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论文类别: Article
英文论文类别: Article
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