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DNA methylation variation along the cancer epigenome and the identification of novel epigenetic driver events
While large-scale studies applying various statistical approaches have identified hundreds of mutated driver genes across various cancer types, the contribution of epigenetic changes to cancer remains more enigmatic. This is partly due to the fact that certain regions of the cancer genome, due to th...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8682778/ https://www.ncbi.nlm.nih.gov/pubmed/34871444 http://dx.doi.org/10.1093/nar/gkab1167 |
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author | Heery, Richard Schaefer, Martin H |
author_facet | Heery, Richard Schaefer, Martin H |
author_sort | Heery, Richard |
collection | PubMed |
description | While large-scale studies applying various statistical approaches have identified hundreds of mutated driver genes across various cancer types, the contribution of epigenetic changes to cancer remains more enigmatic. This is partly due to the fact that certain regions of the cancer genome, due to their genomic and epigenomic properties, are more prone to dysregulated DNA methylation than others. Thus, it has been difficult to distinguish which promoter methylation changes are really driving carcinogenesis from those that are mostly just a reflection of their genomic location. By developing a novel method that corrects for epigenetic covariates, we reveal a small, concise set of potential epigenetic driver events. Interestingly, those changes suggest different modes of epigenetic carcinogenesis: first, we observe recurrent inactivation of known cancer genes across tumour types suggesting a higher convergence on common tumour suppressor pathways than previously anticipated. Second, in prostate cancer, a cancer type with few recurrently mutated genes, we demonstrate how the epigenome primes tumours towards higher tolerance of other aberrations. |
format | Online Article Text |
id | pubmed-8682778 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-86827782021-12-20 DNA methylation variation along the cancer epigenome and the identification of novel epigenetic driver events Heery, Richard Schaefer, Martin H Nucleic Acids Res Computational Biology While large-scale studies applying various statistical approaches have identified hundreds of mutated driver genes across various cancer types, the contribution of epigenetic changes to cancer remains more enigmatic. This is partly due to the fact that certain regions of the cancer genome, due to their genomic and epigenomic properties, are more prone to dysregulated DNA methylation than others. Thus, it has been difficult to distinguish which promoter methylation changes are really driving carcinogenesis from those that are mostly just a reflection of their genomic location. By developing a novel method that corrects for epigenetic covariates, we reveal a small, concise set of potential epigenetic driver events. Interestingly, those changes suggest different modes of epigenetic carcinogenesis: first, we observe recurrent inactivation of known cancer genes across tumour types suggesting a higher convergence on common tumour suppressor pathways than previously anticipated. Second, in prostate cancer, a cancer type with few recurrently mutated genes, we demonstrate how the epigenome primes tumours towards higher tolerance of other aberrations. Oxford University Press 2021-12-06 /pmc/articles/PMC8682778/ /pubmed/34871444 http://dx.doi.org/10.1093/nar/gkab1167 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Computational Biology Heery, Richard Schaefer, Martin H DNA methylation variation along the cancer epigenome and the identification of novel epigenetic driver events |
title | DNA methylation variation along the cancer epigenome and the identification of novel epigenetic driver events |
title_full | DNA methylation variation along the cancer epigenome and the identification of novel epigenetic driver events |
title_fullStr | DNA methylation variation along the cancer epigenome and the identification of novel epigenetic driver events |
title_full_unstemmed | DNA methylation variation along the cancer epigenome and the identification of novel epigenetic driver events |
title_short | DNA methylation variation along the cancer epigenome and the identification of novel epigenetic driver events |
title_sort | dna methylation variation along the cancer epigenome and the identification of novel epigenetic driver events |
topic | Computational Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8682778/ https://www.ncbi.nlm.nih.gov/pubmed/34871444 http://dx.doi.org/10.1093/nar/gkab1167 |
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