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

Kulis, M; Heath, S; Bibikova, M; Queirós, AC; Navarro, A; Clot, G; Martínez-Trillos, A; (2012) Epigenomic analysis detects widespread gene-body DNA hypomethylation in chronic lymphocytic leukemia. Nat Genet , 44 (11) pp. 1236-1242. 10.1038/ng.2443.

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Abstract

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.

Type: Article
Title: Epigenomic analysis detects widespread gene-body DNA hypomethylation in chronic lymphocytic leukemia.
Location: United States
DOI: 10.1038/ng.2443
Publisher version: http://dx.doi.org/10.1038/ng.2443
Keywords: Adult, Aged, Aged, 80 and over, Alternative Splicing, B-Lymphocytes, CpG Islands, DNA Methylation, Epigenesis, Genetic, Female, Gene Expression Regulation, Genome, Human, High-Throughput Nucleotide Sequencing, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Male, Middle Aged
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Wolfson Institute and Cancer Institute Administration > Cancer Institute
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Wolfson Institute and Cancer Institute Administration > Cancer Institute > Research Department of Cancer Biology
URI: http://discovery.ucl.ac.uk/id/eprint/1530103
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