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Hopp L, Löffler-Wirth H, Binder H. Epigenetic Heterogeneity of B-Cell Lymphoma: DNA Methylation, Gene Expression and Chromatin States. Genes (Basel). 2015;6(3):812-40doi: 10.3390/genes6030812.
Hopp, L., Löffler-Wirth, H., & Binder, H. (2015). Epigenetic Heterogeneity of B-Cell Lymphoma: DNA Methylation, Gene Expression and Chromatin States. Genes, 6(3), 812-40. https://doi.org/10.3390/genes6030812
Hopp, Lydia, et al. "Epigenetic Heterogeneity of B-Cell Lymphoma: DNA Methylation, Gene Expression and Chromatin States." Genes vol. 6,3 (2015): 812-40. doi: https://doi.org/10.3390/genes6030812
Hopp L, Löffler-Wirth H, Binder H. Epigenetic Heterogeneity of B-Cell Lymphoma: DNA Methylation, Gene Expression and Chromatin States. Genes (Basel). 2015 Sep 07;6(3):812-40. doi: 10.3390/genes6030812. PMID: 26371046; PMCID: PMC4584331.
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Genes (Basel). 2015 Sep 07;6(3):812-40. doi: 10.3390/genes6030812.

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

Genes

Lydia Hopp, Henry Löffler-Wirth, Hans Binder

Affiliations

  1. Interdisciplinary Centre for Bioinformatics, Universität Leipzig, Härtelstr. 16-18, 04107 Leipzig, Germany. [email protected].
  2. Interdisciplinary Centre for Bioinformatics, Universität Leipzig, Härtelstr. 16-18, 04107 Leipzig, Germany. [email protected].
  3. Interdisciplinary Centre for Bioinformatics, Universität Leipzig, Härtelstr. 16-18, 04107 Leipzig, Germany. [email protected].

PMID: 26371046 PMCID: PMC4584331 DOI: 10.3390/genes6030812

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.

Keywords: epigenetic reprogramming; gene expression; germinal center; high dimensional data portraying; machine learning; promoter methylation; stemness

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