Cargando…

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

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 D...

Descripción completa

Detalles Bibliográficos
Autores principales: Hopp, Lydia, Löffler-Wirth, Henry, Binder, Hans
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4584331/
https://www.ncbi.nlm.nih.gov/pubmed/26371046
http://dx.doi.org/10.3390/genes6030812
_version_ 1782391974862520320
author Hopp, Lydia
Löffler-Wirth, Henry
Binder, Hans
author_facet Hopp, Lydia
Löffler-Wirth, Henry
Binder, Hans
author_sort Hopp, Lydia
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4584331
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-45843312015-10-05 Epigenetic Heterogeneity of B-Cell Lymphoma: DNA Methylation, Gene Expression and Chromatin States Hopp, Lydia Löffler-Wirth, Henry Binder, Hans Genes (Basel) Article 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. MDPI 2015-09-07 /pmc/articles/PMC4584331/ /pubmed/26371046 http://dx.doi.org/10.3390/genes6030812 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hopp, Lydia
Löffler-Wirth, Henry
Binder, Hans
Epigenetic Heterogeneity of B-Cell Lymphoma: DNA Methylation, Gene Expression and Chromatin States
title Epigenetic Heterogeneity of B-Cell Lymphoma: DNA Methylation, Gene Expression and Chromatin States
title_full Epigenetic Heterogeneity of B-Cell Lymphoma: DNA Methylation, Gene Expression and Chromatin States
title_fullStr Epigenetic Heterogeneity of B-Cell Lymphoma: DNA Methylation, Gene Expression and Chromatin States
title_full_unstemmed Epigenetic Heterogeneity of B-Cell Lymphoma: DNA Methylation, Gene Expression and Chromatin States
title_short Epigenetic Heterogeneity of B-Cell Lymphoma: DNA Methylation, Gene Expression and Chromatin States
title_sort epigenetic heterogeneity of b-cell lymphoma: dna methylation, gene expression and chromatin states
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4584331/
https://www.ncbi.nlm.nih.gov/pubmed/26371046
http://dx.doi.org/10.3390/genes6030812
work_keys_str_mv AT hopplydia epigeneticheterogeneityofbcelllymphomadnamethylationgeneexpressionandchromatinstates
AT lofflerwirthhenry epigeneticheterogeneityofbcelllymphomadnamethylationgeneexpressionandchromatinstates
AT binderhans epigeneticheterogeneityofbcelllymphomadnamethylationgeneexpressionandchromatinstates