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Oncogene. 2017 Oct 5;36(40):5648-5657. doi: 10.1038/onc.2017.176. Epub 2017 Jun 5.

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

Author information

1
Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
2
Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
3
Universitat Pompeu Fabra (UPF), Barcelona, Spain.
4
CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
5
Biomedical Genomics Lab, Research Program on Biomedical Informatics, IMIM Hospital del Mar Medical Research Institute and Universitat Pompeu Fabra, Barcelona, Spain.
6
Joint IRB-BSC Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
7
Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain.
8
Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain.
9
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
10
Department of Physiological Sciences II, School of Medicine, University of Barcelona, Barcelona, Spain.

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.

PMID:
28581523
PMCID:
PMC5633654
DOI:
10.1038/onc.2017.176
[Indexed for MEDLINE]
Free PMC Article

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