Vidal Ocabo, EnriqueSayols, SergiMoran, SebastianGuillaumet-Adkins, AmySchroeder, Michael Philipp, 1986-Royo, RominaOrozco, ModestoGut, MartaGut, Ivo GlynneLópez Bigas, NúriaHeyn, HolgerEsteller, Manel2018-01-192018-01-192017Vidal 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):5648-57. DOI: 10.1038/onc.2017.1760950-9232http://hdl.handle.net/10230/33697Although 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.application/pdfeng© 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/info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/onc.2017.176DNA MethylationBase pairingNeoplasminfo:eu-repo/semantics/openAccess