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Genes 2015, 6(3), 812-840; doi:10.3390/genes6030812

Epigenetic Heterogeneity of B-Cell Lymphoma: DNA Methylation, Gene Expression and Chromatin States

Interdisciplinary Centre for Bioinformatics, Universität Leipzig, Härtelstr. 16–18, 04107 Leipzig, Germany
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Academic Editor: Jessica Tyler
Received: 30 April 2015 / Accepted: 18 August 2015 / Published: 7 September 2015
(This article belongs to the Special Issue Chromatin Dynamics)
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Abstract

Mature B-cell lymphoma is a clinically and biologically highly diverse disease. Its diagnosis and prognosis is a challenge due to its molecular heterogeneity and diverse regimes of biological dysfunctions, which are partly driven by epigenetic mechanisms. We here present an integrative analysis of DNA methylation and gene expression data of several lymphoma subtypes. Our study confirms previous results about the role of stemness genes during development and maturation of B-cells and their dysfunction in lymphoma locking in more proliferative or immune-reactive states referring to B-cell functionalities in the dark and light zone of the germinal center and also in plasma cells. These dysfunctions are governed by widespread epigenetic effects altering the promoter methylation of the involved genes, their activity status as moderated by histone modifications and also by chromatin remodeling. We identified four groups of genes showing characteristic expression and methylation signatures among Burkitt’s lymphoma, diffuse large B cell lymphoma, follicular lymphoma and multiple myeloma. These signatures are associated with epigenetic effects such as remodeling from transcriptionally inactive into active chromatin states, differential promoter methylation and the enrichment of targets of transcription factors such as EZH2 and SUZ12. View Full-Text
Keywords: germinal center; epigenetic reprogramming; stemness; promoter methylation; gene expression; machine learning; high dimensional data portraying germinal center; epigenetic reprogramming; stemness; promoter methylation; gene expression; machine learning; high dimensional data portraying
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Hopp, L.; Löffler-Wirth, H.; Binder, H. Epigenetic Heterogeneity of B-Cell Lymphoma: DNA Methylation, Gene Expression and Chromatin States. Genes 2015, 6, 812-840.

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