DNA Methylation Patterns in Normal Tissue Correlate more Strongly with Breast Cancer Status than Copy-Number Variants

DNA Methylation Patterns in Normal Tissue Correlate more Strongly with Breast Cancer Status than Copy-Number Variants

Normal tissue at risk of neoplastic transformation is characterized by somatic mutations, copy-number variation and DNA methylation changes. It is unclear however, which type of alteration may be more informative of cancer risk. We analyzed genome-wide DNA methylation and copy-number calls from the...

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Main Authors: Yang Gao, Martin Widschwendter, Andrew E. Teschendorff
Format: Article
Language:English
Published: Elsevier 2018-05-01
Series:EBioMedicine
Online Access:http://www.sciencedirect.com/science/article/pii/S2352396418301531
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spelling doaj-6263198cee43415893b718198dfbdfda2020-11-25T02:01:56ZengElsevierEBioMedicine2352-39642018-05-0131243252DNA Methylation Patterns in Normal Tissue Correlate more Strongly with Breast Cancer Status than Copy-Number VariantsYang Gao0Martin Widschwendter1Andrew E. Teschendorff2CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institute for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, ChinaDepartment of Women's Cancer, University College London, 74 Huntley Street, London WC1E 6AU, United KingdomCAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institute for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China; Department of Women's Cancer, University College London, 74 Huntley Street, London WC1E 6AU, United Kingdom; UCL Cancer Institute, Paul O'Gorman Building, University College London, 72 Huntley Street, London WC1E 6BT, United Kingdom; Corresponding author at: CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institute for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.Normal tissue at risk of neoplastic transformation is characterized by somatic mutations, copy-number variation and DNA methylation changes. It is unclear however, which type of alteration may be more informative of cancer risk. We analyzed genome-wide DNA methylation and copy-number calls from the same DNA assay in a cohort of healthy breast samples and age-matched normal samples collected adjacent to breast cancer. Using statistical methods to adjust for cell type heterogeneity, we show that DNA methylation changes can discriminate normal-adjacent from normal samples better than somatic copy-number variants. We validate this important finding in an independent dataset. These results suggest that DNA methylation alterations in the normal cell of origin may offer better cancer risk prediction and early detection markers than copy-number changes. Keywords: Cancer, Cancer-risk, Early detection, DNA methylation, Epigenetic, Copy-number, Breast cancerhttp://www.sciencedirect.com/science/article/pii/S2352396418301531
collection DOAJ
language English
format Article
sources DOAJ
author Yang Gao
Martin Widschwendter
Andrew E. Teschendorff
spellingShingle Yang Gao
Martin Widschwendter
Andrew E. Teschendorff
DNA Methylation Patterns in Normal Tissue Correlate more Strongly with Breast Cancer Status than Copy-Number Variants
EBioMedicine
author_facet Yang Gao
Martin Widschwendter
Andrew E. Teschendorff
author_sort Yang Gao
title DNA Methylation Patterns in Normal Tissue Correlate more Strongly with Breast Cancer Status than Copy-Number Variants
title_short DNA Methylation Patterns in Normal Tissue Correlate more Strongly with Breast Cancer Status than Copy-Number Variants
title_full DNA Methylation Patterns in Normal Tissue Correlate more Strongly with Breast Cancer Status than Copy-Number Variants
title_fullStr DNA Methylation Patterns in Normal Tissue Correlate more Strongly with Breast Cancer Status than Copy-Number Variants
title_full_unstemmed DNA Methylation Patterns in Normal Tissue Correlate more Strongly with Breast Cancer Status than Copy-Number Variants
title_sort dna methylation patterns in normal tissue correlate more strongly with breast cancer status than copy-number variants
publisher Elsevier
series EBioMedicine
issn 2352-3964
publishDate 2018-05-01
description Normal tissue at risk of neoplastic transformation is characterized by somatic mutations, copy-number variation and DNA methylation changes. It is unclear however, which type of alteration may be more informative of cancer risk. We analyzed genome-wide DNA methylation and copy-number calls from the same DNA assay in a cohort of healthy breast samples and age-matched normal samples collected adjacent to breast cancer. Using statistical methods to adjust for cell type heterogeneity, we show that DNA methylation changes can discriminate normal-adjacent from normal samples better than somatic copy-number variants. We validate this important finding in an independent dataset. These results suggest that DNA methylation alterations in the normal cell of origin may offer better cancer risk prediction and early detection markers than copy-number changes. Keywords: Cancer, Cancer-risk, Early detection, DNA methylation, Epigenetic, Copy-number, Breast cancer
url http://www.sciencedirect.com/science/article/pii/S2352396418301531
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AT martinwidschwendter dnamethylationpatternsinnormaltissuecorrelatemorestronglywithbreastcancerstatusthancopynumbervariants
AT andreweteschendorff dnamethylationpatternsinnormaltissuecorrelatemorestronglywithbreastcancerstatusthancopynumbervariants
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