Epigenomic analysis detects widespread gene-body DNA hypomethylation in chronic lymphocytic leukemia.
|Title||Epigenomic analysis detects widespread gene-body DNA hypomethylation in chronic lymphocytic leukemia.|
|Publication Type||Journal Article|
|Year of Publication||2012|
|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, 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.|
|Date Published||2012 Nov|
|Keywords||80 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.