Aberration in DNA Methylation in B-Cell Lymphomas Has a Complex Origin and Increases with Disease Severity

• DOI: 10.1371/journal.pgen.1003137
• Publication Date: 2013-01-10T21:50:59Z
• Authors: Subhajyoti De; Rita Shaknovich; Markus Riester; Olivier Elemento; Huimin Geng; Matthias Kormaksson; Yanwen Jiang; Bruce Woolcock; Nathalie Johnson; Jose M. Polo; Leandro Cerchietti; Randy D. Gascoyne; Ari Melnick; Franziska Michor
• Keywords: CTCF

Despite mounting evidence that epigenetic abnormalities play a key role in cancer biology, their contributions to the malignant phenotype remain poorly understood. Here we studied genome-wide DNA methylation normal B-cell populations and subtypes of non-Hodgkin lymphoma: follicular lymphoma diffuse large lymphomas. These lymphomas display striking progressive intra-tumor heterogeneity also inter-patient cytosine patterns. Epigenetic is initiated germinal center B-cells, increases markedly with disease aggressiveness, associated unfavorable clinical outcome. Moreover, patterns abnormal vary depending upon chromosomal regions, gene density status neighboring genes. arise via two distinct processes: i) lymphomagenic transcriptional regulators perturb promoter target gene-specific manner, ii) aberrant states tend spread promoters absence CTCF insulator binding sites.