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- Title
Epigenomic analysis detects widespread gene-body DNA hypomethylation in chronic lymphocytic leukemia.
- Authors
Kulis, Marta; Heath, Simon; Bibikova, Marina; Queirós, Ana C; Navarro, Alba; Clot, Guillem; Martínez-Trillos, Alejandra; Castellano, Giancarlo; Brun-Heath, Isabelle; Pinyol, Magda; Barberán-Soler, Sergio; Papasaikas, Panagiotis; Jares, Pedro; Beà, Sílvia; Rico, Daniel; Ecker, Simone; Rubio, Miriam; Royo, Romina; Ho, Vincent; Klotzle, Brandy
- 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.
- Subjects
DNA methylation; CHRONIC lymphocytic leukemia; B cells; POPULATION genetics; DNA microarrays; GENE expression
- Publication
Nature Genetics, 2012, Vol 44, Issue 11, p1236
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.2443