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A DNA methylation map of human cancer at single base-pair resolution

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dc.contributor.author Vidal Ocabo, Enrique
dc.contributor.author Sayols, Sergi
dc.contributor.author Moran, Sebastian
dc.contributor.author Guillaumet-Adkins, Amy
dc.contributor.author Schroeder, Michael Philipp, 1986-
dc.contributor.author Royo, Romina
dc.contributor.author Orozco, Modesto
dc.contributor.author Gut, Marta
dc.contributor.author Gut, Ivo Glynne
dc.contributor.author López Bigas, Núria
dc.contributor.author Heyn, Holger
dc.contributor.author Esteller, Manel
dc.date.accessioned 2018-01-19T11:19:22Z
dc.date.available 2018-01-19T11:19:22Z
dc.date.issued 2017
dc.identifier.citation Vidal E, Sayols S, Moran S, Guillaumet-Adkins A, Schroeder MP, Royo R et al. A DNA methylation map of human cancer at single base-pair resolution. Oncogene. 2017 Oct 5;36(40):5648-5657. DOI: 10.1038/onc.2017.176
dc.identifier.issn 0950-9232
dc.identifier.uri http://hdl.handle.net/10230/33697
dc.description.abstract Although single base-pair resolution DNA methylation landscapes for embryonic and different somatic cell types provided important insights into epigenetic dynamics and cell-type specificity, such comprehensive profiling is incomplete across human cancer types. This prompted us to perform genome-wide DNA methylation profiling of 22 samples derived from normal tissues and associated neoplasms, including primary tumors and cancer cell lines. Unlike their invariant normal counterparts, cancer samples exhibited highly variable CpG methylation levels in a large proportion of the genome, involving progressive changes during tumor evolution. The whole-genome sequencing results from selected samples were replicated in a large cohort of 1112 primary tumors of various cancer types using genome-scale DNA methylation analysis. Specifically, we determined DNA hypermethylation of promoters and enhancers regulating tumor-suppressor genes, with potential cancer-driving effects. DNA hypermethylation events showed evidence of positive selection, mutual exclusivity and tissue specificity, suggesting their active participation in neoplastic transformation. Our data highlight the extensive changes in DNA methylation that occur in cancer onset, progression and dissemination.
dc.description.sponsorship This work was supported by Institute of Health Carlos III ISCIII Project no. PI11/00321, Spanish Cancer Research Network (RTICC) no. RD12/0036/0039; European Development Regional Fund, ‘A way to achieve Europe’ ERDF (SAF2014-55000-R), Sandra Ibarra Foundation; Olga Torres Foundation; Cellex Foundation; AGAUR 2014SGR633 grant; Health and Science Departments of the Catalan government (Generalitat de Catalunya) and European Community's Seventh Framework Program (FP7/2007-2013), grant HEALTH-F5-2011-282510 – BLUEPRINT. HH is a Miguel Servet (CP14/00229) ISCII researcher.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Nature Publishing Group
dc.relation.ispartof Oncogene. 2017 Oct 5;36(40):5648-5657
dc.rights © Nature Publishing Group. http://dx.doi.org/10.1038/onc.2017.176 This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title A DNA methylation map of human cancer at single base-pair resolution
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1038/onc.2017.176
dc.subject.keyword DNA Methylation
dc.subject.keyword Base pairing
dc.subject.keyword Neoplasm
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/282510
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2014-55000-R
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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