Dataset Information

DNA methylome analysis in Burkitt and follicular lymphomas identifies differentially methylated regions linked to somatic mutation and transcriptional control.

ABSTRACT: Although Burkitt lymphomas and follicular lymphomas both have features of germinal center B cells, they are biologically and clinically quite distinct. Here we performed whole-genome bisulfite, genome and transcriptome sequencing in 13 IG-MYC translocation-positive Burkitt lymphoma, nine BCL2 translocation-positive follicular lymphoma and four normal germinal center B cell samples. Comparison of Burkitt and follicular lymphoma samples showed differential methylation of intragenic regions that strongly correlated with expression of associated genes, for example, genes active in germinal center dark-zone and light-zone B cells. Integrative pathway analyses of regions differentially methylated in Burkitt and follicular lymphomas implicated DNA methylation as cooperating with somatic mutation of sphingosine phosphate signaling, as well as the TCF3-ID3 and SWI/SNF complexes, in a large fraction of Burkitt lymphomas. Taken together, our results demonstrate a tight connection between somatic mutation, DNA methylation and transcriptional control in key B cell pathways deregulated differentially in Burkitt lymphoma and other germinal center B cell lymphomas.

SUBMITTER: Kretzmer H

PROVIDER: S-EPMC5444523 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

DNA methylome analysis in Burkitt and follicular lymphomas identifies differentially methylated regions linked to somatic mutation and transcriptional control.

Kretzmer Helene H Bernhart Stephan H SH Wang Wei W Haake Andrea A Weniger Marc A MA Bergmann Anke K AK Betts Matthew J MJ Carrillo-de-Santa-Pau Enrique E Doose Gero G Gutwein Jana J Richter Julia J Hovestadt Volker V Huang Bingding B Rico Daniel D Jühling Frank F Kolarova Julia J Lu Qianhao Q Otto Christian C Wagener Rabea R Arnolds Judith J Burkhardt Birgit B Claviez Alexander A Drexler Hans G HG Eberth Sonja S Eils Roland R Flicek Paul P Haas Siegfried S Humme Michael M Karsch Dennis D Kerstens Hinrik H D HHD Klapper Wolfram W Kreuz Markus M Lawerenz Chris C Lenzek Dido D Loeffler Markus M López Cristina C MacLeod Roderick A F RAF Martens Joost H A JHA Kulis Marta M Martín-Subero José Ignacio JI Möller Peter P Nage Inga I Picelli Simone S Vater Inga I Rohde Marius M Rosenstiel Philip P Rosolowski Maciej M Russell Robert B RB Russell Robert B RB Schilhabel Markus M Schlesner Matthias M Stadler Peter F PF Szczepanowski Monika M Trümper Lorenz L Stunnenberg Hendrik G HG Küppers Ralf R Ammerpohl Ole O Lichter Peter P Siebert Reiner R Hoffmann Steve S Radlwimmer Bernhard B

Nature genetics 20151005 11

Although Burkitt lymphomas and follicular lymphomas both have features of germinal center B cells, they are biologically and clinically quite distinct. Here we performed whole-genome bisulfite, genome and transcriptome sequencing in 13 IG-MYC translocation-positive Burkitt lymphoma, nine BCL2 translocation-positive follicular lymphoma and four normal germinal center B cell samples. Comparison of Burkitt and follicular lymphoma samples showed differential methylation of intragenic regions that st ...[more]

PMID: 26437030

Similar Datasets

Project description:BackgroundGrowing evidence shows that epigenetic modifications play a role in Alzheimer's disease (AD). We performed an epigenome-wide association study (EWAS) to evaluate the DNA methylation differences using postmortem superior temporal gyrus (STG) and inferior frontal gyrus (IFG) samples.ResultsSamples from 72 AD patients and 62 age-matched cognitively normal controls were assayed using Illumina© Infinium MethylationEPIC BeadChip. Five and 14 differentially methylated positions (DMPs) associated with pathology (i.e., Braak stage) with p value less than Bonferroni correction threshold of 6.79 × 10-8 in the STG and IFG were identified, respectively. These cytosine-phosphate-guanine (CpG) sites included promoter associated cg26263477 annotated to ABCA7 in the STG (p = 1.21 × 10-11), and cg14058329 annotated to the HOXA5/HOXA3/HOXA-AS3 gene cluster (p = 1.62 × 10-9) and cg09448088 (p = 3.95 × 10-9) annotated to MCF2L in the IFG. These genes were previously reported to harbor DMPs and/or differentially methylated regions (DMRs). Previously reported DMPs annotated to RMGA, GNG7, HOXA3, GPR56, SPG7, PCNT, RP11-961A15.1, MCF2L, RHBDF2, ANK1, PCNT, TPRG1, and RASGEF1C were replicated (p < 0.0001). One hundred twenty-one and 173 DMRs associated with pathology in the STG and IFG, respectively, were additionally identified. Of these, DMRs annotated to 30 unique genes were also identified as significant DMRs in the same brain region in a recent meta-analysis, while additional DMRs annotated to 12 genes were reported as DMRs in a different brain region or in a cross-cortex meta-analysis. The significant DMRs were enriched in promoters, CpG islands, and exons in the genome. Gene set enrichment analysis of DMPs and DMRs showed that gene sets involved in neuroinflammation (e.g., microglia differentiation), neurogenesis, and cognition were enriched (false discovery rate (FDR) < 0.05).ConclusionsTwenty-two DMPs and 30 DMRs associated with pathology were replicated, and novel DMPs and DMRs were discovered.

Dataset Information

DNA methylome analysis in Burkitt and follicular lymphomas identifies differentially methylated regions linked to somatic mutation and transcriptional control.

Publications

DNA methylome analysis in Burkitt and follicular lymphomas identifies differentially methylated regions linked to somatic mutation and transcriptional control.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets