Epigenomic analysis detects widespread gene-body DNA hypomethylation in chronic lymphocytic leukemia

By M. Kulis, S. Heath, M. Bibikova, A. Queirós, A. Navarro, G. Clot, A. Martínez‐Trillos, G. Castellano, I. Brun-Heath, M. Pinyol and 31 more. Nature Genetics, 2012

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We have extensively characterized the DNA methylomes of 139 patients with chronic lymphocytic leukemia (CLL) with mutated or unmutated IGHV and of several mature B-cell subpopulations through the use of whole-genome bisulfite sequencing and high-density microarrays. The two molecular subtypes of CLL have differing DNA methylomes that seem to represent epigenetic imprints from distinct normal B-cell subpopulations. DNA hypomethylation in the gene body, targeting mostly enhancer sites, was the most frequent difference between naive and memory B cells and between the two molecular subtypes of CLL and normal B cells. Although DNA methylation and gene expression were poorly correlated, we identified gene-body CpG dinucleotides whose methylation was positively or negatively associated with expression. We have also recognized a DNA methylation signature that distinguishes new clinico-biological subtypes of CLL. We propose an epigenomic scenario in which differential methylation in the gene body may have functional and clinical implications in leukemogenesis.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/86c9f0c83b30a4ccdc98ddb5bfc2a3601094b983

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