The dynamics of DNA methylation covariation patterns in carcinogenesis.

Recently it has been observed that cancer tissue is characterised by an increased variability in DNA methylation patterns. However, how the correlative patterns in genome-wide DNA methylation change during the carcinogenic progress has not yet been explored. Here we study genome-wide inter-CpG corre...

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Autores principales:	Andrew E Teschendorff, Xiaoping Liu, Helena Caren, Steve M Pollard, Stephan Beck, Martin Widschwendter, Luonan Chen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/9bf8292883f84c2aa825e8947f100590
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spelling	oai:doaj.org-article:9bf8292883f84c2aa825e8947f1005902021-11-25T05:40:59ZThe dynamics of DNA methylation covariation patterns in carcinogenesis.1553-734X1553-735810.1371/journal.pcbi.1003709https://doaj.org/article/9bf8292883f84c2aa825e8947f1005902014-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25010556/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Recently it has been observed that cancer tissue is characterised by an increased variability in DNA methylation patterns. However, how the correlative patterns in genome-wide DNA methylation change during the carcinogenic progress has not yet been explored. Here we study genome-wide inter-CpG correlations in DNA methylation, in addition to single site variability, during cervical carcinogenesis. We demonstrate how the study of changes in DNA methylation covariation patterns across normal, intra-epithelial neoplasia and invasive cancer allows the identification of CpG sites that indicate the risk of neoplastic transformation in stages prior to neoplasia. Importantly, we show that the covariation in DNA methylation at these risk CpG loci is maximal immediately prior to the onset of cancer, supporting the view that high epigenetic diversity in normal cells increases the risk of cancer. Consistent with this, we observe that invasive cancers exhibit increased covariation in DNA methylation at the risk CpG sites relative to normal tissue, but lower levels relative to pre-cancerous lesions. We further show that the identified risk CpG sites undergo preferential DNA methylation changes in relation to human papilloma virus infection and age. Results are validated in independent data including prospectively collected samples prior to neoplastic transformation. Our data are consistent with a phase transition model of carcinogenesis, in which epigenetic diversity is maximal prior to the onset of cancer. The model and algorithm proposed here may allow, in future, network biomarkers predicting the risk of neoplastic transformation to be identified.Andrew E TeschendorffXiaoping LiuHelena CarenSteve M PollardStephan BeckMartin WidschwendterLuonan ChenPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 10, Iss 7, p e1003709 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Andrew E Teschendorff Xiaoping Liu Helena Caren Steve M Pollard Stephan Beck Martin Widschwendter Luonan Chen The dynamics of DNA methylation covariation patterns in carcinogenesis.
description	Recently it has been observed that cancer tissue is characterised by an increased variability in DNA methylation patterns. However, how the correlative patterns in genome-wide DNA methylation change during the carcinogenic progress has not yet been explored. Here we study genome-wide inter-CpG correlations in DNA methylation, in addition to single site variability, during cervical carcinogenesis. We demonstrate how the study of changes in DNA methylation covariation patterns across normal, intra-epithelial neoplasia and invasive cancer allows the identification of CpG sites that indicate the risk of neoplastic transformation in stages prior to neoplasia. Importantly, we show that the covariation in DNA methylation at these risk CpG loci is maximal immediately prior to the onset of cancer, supporting the view that high epigenetic diversity in normal cells increases the risk of cancer. Consistent with this, we observe that invasive cancers exhibit increased covariation in DNA methylation at the risk CpG sites relative to normal tissue, but lower levels relative to pre-cancerous lesions. We further show that the identified risk CpG sites undergo preferential DNA methylation changes in relation to human papilloma virus infection and age. Results are validated in independent data including prospectively collected samples prior to neoplastic transformation. Our data are consistent with a phase transition model of carcinogenesis, in which epigenetic diversity is maximal prior to the onset of cancer. The model and algorithm proposed here may allow, in future, network biomarkers predicting the risk of neoplastic transformation to be identified.
format	article
author	Andrew E Teschendorff Xiaoping Liu Helena Caren Steve M Pollard Stephan Beck Martin Widschwendter Luonan Chen
author_facet	Andrew E Teschendorff Xiaoping Liu Helena Caren Steve M Pollard Stephan Beck Martin Widschwendter Luonan Chen
author_sort	Andrew E Teschendorff
title	The dynamics of DNA methylation covariation patterns in carcinogenesis.
title_short	The dynamics of DNA methylation covariation patterns in carcinogenesis.
title_full	The dynamics of DNA methylation covariation patterns in carcinogenesis.
title_fullStr	The dynamics of DNA methylation covariation patterns in carcinogenesis.
title_full_unstemmed	The dynamics of DNA methylation covariation patterns in carcinogenesis.
title_sort	dynamics of dna methylation covariation patterns in carcinogenesis.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/9bf8292883f84c2aa825e8947f100590
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The dynamics of DNA methylation covariation patterns in carcinogenesis.

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