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

TitleEpigenomic analysis detects widespread gene-body DNA hypomethylation in chronic lymphocytic leukemia.
Publication TypeJournal Article
Year of Publication2012
AuthorsKulis, 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, Hernández Lluis, Conde Laura, López-Guerra Mónica, Colomer Dolors, Villamor Neus, Aymerich Marta, Rozman María, Bayes Mónica, Gut Marta, Gelpí Josep-Lluis, Orozco Modesto, Fan Jian-Bing, Quesada Víctor, Puente Xose S., Pisano David G., Valencia Alfonso, López-Guillermo Armando, Gut Ivo, López-Otín Carlos, Campo Elías, and Martín-Subero José I.
JournalNat Genet
Date Published2012 Nov
Keywords80 and over, Adult, Aged, Alternative Splicing, B-Cell, B-Lymphocytes, Chronic, CpG Islands, DNA Methylation, Epigenesis, Female, Gene Expression Regulation, Genetic, Genome, High-Throughput Nucleotide Sequencing, Human, Humans, Leukemia, Lymphocytic, Male, Middle Aged

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.