Corruption of the intra-gene DNA methylation architecture is a hallmark of cancer.

Epigenetic processes--including DNA methylation--are increasingly seen as having a fundamental role in chronic diseases like cancer. It is well known that methylation levels at particular genes or loci differ between normal and diseased tissue. Here we investigate whether the intra-gene methylation...

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Autores principales:	Thomas E Bartlett, Alexey Zaikin, Sofia C Olhede, James West, Andrew E Teschendorff, Martin Widschwendter
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6cd3b9f19a8540cd8d21a45df7454836
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spelling	oai:doaj.org-article:6cd3b9f19a8540cd8d21a45df74548362021-11-18T07:37:35ZCorruption of the intra-gene DNA methylation architecture is a hallmark of cancer.1932-620310.1371/journal.pone.0068285https://doaj.org/article/6cd3b9f19a8540cd8d21a45df74548362013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23874574/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Epigenetic processes--including DNA methylation--are increasingly seen as having a fundamental role in chronic diseases like cancer. It is well known that methylation levels at particular genes or loci differ between normal and diseased tissue. Here we investigate whether the intra-gene methylation architecture is corrupted in cancer and whether the variability of levels of methylation of individual CpGs within a defined gene is able to discriminate cancerous from normal tissue, and is associated with heterogeneous tumour phenotype, as defined by gene expression. We analysed 270985 CpGs annotated to 18272 genes, in 3284 cancerous and 681 normal samples, corresponding to 14 different cancer types. In doing so, we found novel differences in intra-gene methylation pattern across phenotypes, particularly in those genes which are crucial for stem cell biology; our measures of intra-gene methylation architecture are a better determinant of phenotype than measures based on mean methylation level alone (K-S test [Formula: see text] in all 14 diseases tested). These per-gene methylation measures also represent a considerable reduction in complexity, compared to conventional per-CpG beta-values. Our findings strongly support the view that intra-gene methylation architecture has great clinical potential for the development of DNA-based cancer biomarkers.Thomas E BartlettAlexey ZaikinSofia C OlhedeJames WestAndrew E TeschendorffMartin WidschwendterPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e68285 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Thomas E Bartlett Alexey Zaikin Sofia C Olhede James West Andrew E Teschendorff Martin Widschwendter Corruption of the intra-gene DNA methylation architecture is a hallmark of cancer.
description	Epigenetic processes--including DNA methylation--are increasingly seen as having a fundamental role in chronic diseases like cancer. It is well known that methylation levels at particular genes or loci differ between normal and diseased tissue. Here we investigate whether the intra-gene methylation architecture is corrupted in cancer and whether the variability of levels of methylation of individual CpGs within a defined gene is able to discriminate cancerous from normal tissue, and is associated with heterogeneous tumour phenotype, as defined by gene expression. We analysed 270985 CpGs annotated to 18272 genes, in 3284 cancerous and 681 normal samples, corresponding to 14 different cancer types. In doing so, we found novel differences in intra-gene methylation pattern across phenotypes, particularly in those genes which are crucial for stem cell biology; our measures of intra-gene methylation architecture are a better determinant of phenotype than measures based on mean methylation level alone (K-S test [Formula: see text] in all 14 diseases tested). These per-gene methylation measures also represent a considerable reduction in complexity, compared to conventional per-CpG beta-values. Our findings strongly support the view that intra-gene methylation architecture has great clinical potential for the development of DNA-based cancer biomarkers.
format	article
author	Thomas E Bartlett Alexey Zaikin Sofia C Olhede James West Andrew E Teschendorff Martin Widschwendter
author_facet	Thomas E Bartlett Alexey Zaikin Sofia C Olhede James West Andrew E Teschendorff Martin Widschwendter
author_sort	Thomas E Bartlett
title	Corruption of the intra-gene DNA methylation architecture is a hallmark of cancer.
title_short	Corruption of the intra-gene DNA methylation architecture is a hallmark of cancer.
title_full	Corruption of the intra-gene DNA methylation architecture is a hallmark of cancer.
title_fullStr	Corruption of the intra-gene DNA methylation architecture is a hallmark of cancer.
title_full_unstemmed	Corruption of the intra-gene DNA methylation architecture is a hallmark of cancer.
title_sort	corruption of the intra-gene dna methylation architecture is a hallmark of cancer.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/6cd3b9f19a8540cd8d21a45df7454836
work_keys_str_mv	AT thomasebartlett corruptionoftheintragenednamethylationarchitectureisahallmarkofcancer AT alexeyzaikin corruptionoftheintragenednamethylationarchitectureisahallmarkofcancer AT sofiacolhede corruptionoftheintragenednamethylationarchitectureisahallmarkofcancer AT jameswest corruptionoftheintragenednamethylationarchitectureisahallmarkofcancer AT andreweteschendorff corruptionoftheintragenednamethylationarchitectureisahallmarkofcancer AT martinwidschwendter corruptionoftheintragenednamethylationarchitectureisahallmarkofcancer
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Corruption of the intra-gene DNA methylation architecture is a hallmark of cancer.

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