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

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

doi:10.1038/ng.3413

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

Helene Kretzmer, Stephan H. Bernhart, Wei Wang, Andrea Haake, Marc A. Weniger, Anke K. Bergmann, Matthew J. Betts, Enrique Carrillo-de-Santa-Pau, Gero Doose, Jana Gutwein, Julia Richter, Volker Hovestadt, Bingding Huang, Daniel Rico, Frank Jühling, Julia Kolarova, Qianhao Lu, Christian Otto, Rabea Wagener, Judith ArnoldsBirgit Burkhardt, Alexander Claviez, Hans G. Drexler, Sonja Eberth, Roland Eils, Paul Flicek, Siegfried Haas, Michael Hummel, Dennis Karsch, Hinrik H.D. Kerstens, Wolfram Klapper, Markus Kreuz, Chris Lawerenz, Dido Lenze, Markus Loeffler, Cristina López, Roderick A.F. MacLeod, Joost H.A. Martens, Marta Kulis, José Ignacio Martín-Subero, Peter Möller, Inga Nagel, Simone Picelli, Inga Vater, Marius Rohde, Philip Rosenstiel, Maciej Rosolowski, Robert B. Russell, Markus Schilhabel, Matthias Schlesner, Peter F. Stadler, Monika Szczepanowski, Lorenz Trümper, Hendrik G. Stunnenberg, Ralf Küppers, Ole Ammerpohl, Peter Lichter, Reiner Siebert, Steve Hoffmann, Bernhard Radlwimmer

Research output: Contribution to journal › Article › peer-review

120 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1316-1325
Number of pages	10
Journal	Nature Genetics
Volume	47
Issue number	11
DOIs	https://doi.org/10.1038/ng.3413
Publication status	Published - 1 Nov 2015
Externally published	Yes

Access to Document

10.1038/ng.3413

Cite this

Kretzmer, H., Bernhart, S. H., Wang, W., Haake, A., Weniger, M. A., Bergmann, A. K., Betts, M. J., Carrillo-de-Santa-Pau, E., Doose, G., Gutwein, J., Richter, J., Hovestadt, V., Huang, B., Rico, D., Jühling, F., Kolarova, J., Lu, Q., Otto, C., Wagener, R., ... Radlwimmer, B. (2015). DNA methylome analysis in Burkitt and follicular lymphomas identifies differentially methylated regions linked to somatic mutation and transcriptional control. Nature Genetics, 47(11), 1316-1325. https://doi.org/10.1038/ng.3413

@article{9fa2bfcee10f417595b77d1732f13d2c,

title = "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.",

author = "Helene Kretzmer and Bernhart, {Stephan H.} and Wei Wang and Andrea Haake and Weniger, {Marc A.} and Bergmann, {Anke K.} and Betts, {Matthew J.} and Enrique Carrillo-de-Santa-Pau and Gero Doose and Jana Gutwein and Julia Richter and Volker Hovestadt and Bingding Huang and Daniel Rico and Frank J{\"u}hling and Julia Kolarova and Qianhao Lu and Christian Otto and Rabea Wagener and Judith Arnolds and Birgit Burkhardt and Alexander Claviez and Drexler, {Hans G.} and Sonja Eberth and Roland Eils and Paul Flicek and Siegfried Haas and Michael Hummel and Dennis Karsch and Kerstens, {Hinrik H.D.} and Wolfram Klapper and Markus Kreuz and Chris Lawerenz and Dido Lenze and Markus Loeffler and Cristina L{\'o}pez and MacLeod, {Roderick A.F.} and Martens, {Joost H.A.} and Marta Kulis and Mart{\'i}n-Subero, {Jos{\'e} Ignacio} and Peter M{\"o}ller and Inga Nagel and Simone Picelli and Inga Vater and Marius Rohde and Philip Rosenstiel and Maciej Rosolowski and Russell, {Robert B.} and Markus Schilhabel and Matthias Schlesner and Stadler, {Peter F.} and Monika Szczepanowski and Lorenz Tr{\"u}mper and Stunnenberg, {Hendrik G.} and Ralf K{\"u}ppers and Ole Ammerpohl and Peter Lichter and Reiner Siebert and Steve Hoffmann and Bernhard Radlwimmer",

note = "Publisher Copyright: {\textcopyright} 2015 Nature America, Inc.",

year = "2015",

month = nov,

day = "1",

doi = "10.1038/ng.3413",

language = "English",

volume = "47",

pages = "1316--1325",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "11",

}

Kretzmer, H, Bernhart, SH, Wang, W, Haake, A, Weniger, MA, Bergmann, AK, Betts, MJ, Carrillo-de-Santa-Pau, E, Doose, G, Gutwein, J, Richter, J, Hovestadt, V, Huang, B, Rico, D, Jühling, F, Kolarova, J, Lu, Q, Otto, C, Wagener, R, Arnolds, J, Burkhardt, B, Claviez, A, Drexler, HG, Eberth, S, Eils, R, Flicek, P, Haas, S, Hummel, M, Karsch, D, Kerstens, HHD, Klapper, W, Kreuz, M, Lawerenz, C, Lenze, D, Loeffler, M, López, C, MacLeod, RAF, Martens, JHA, Kulis, M, Martín-Subero, JI, Möller, P, Nagel, I, Picelli, S, Vater, I, Rohde, M, Rosenstiel, P, Rosolowski, M, Russell, RB, Schilhabel, M, Schlesner, M, Stadler, PF, Szczepanowski, M, Trümper, L, Stunnenberg, HG, Küppers, R, Ammerpohl, O, Lichter, P, Siebert, R, Hoffmann, S & Radlwimmer, B 2015, 'DNA methylome analysis in Burkitt and follicular lymphomas identifies differentially methylated regions linked to somatic mutation and transcriptional control', Nature Genetics, vol. 47, no. 11, pp. 1316-1325. https://doi.org/10.1038/ng.3413

TY - JOUR

T1 - DNA methylome analysis in Burkitt and follicular lymphomas identifies differentially methylated regions linked to somatic mutation and transcriptional control

AU - Kretzmer, Helene

AU - Bernhart, Stephan H.

AU - Wang, Wei

AU - Haake, Andrea

AU - Weniger, Marc A.

AU - Bergmann, Anke K.

AU - Betts, Matthew J.

AU - Carrillo-de-Santa-Pau, Enrique

AU - Doose, Gero

AU - Gutwein, Jana

AU - Richter, Julia

AU - Hovestadt, Volker

AU - Huang, Bingding

AU - Rico, Daniel

AU - Jühling, Frank

AU - Kolarova, Julia

AU - Lu, Qianhao

AU - Otto, Christian

AU - Wagener, Rabea

AU - Arnolds, Judith

AU - Burkhardt, Birgit

AU - Claviez, Alexander

AU - Drexler, Hans G.

AU - Eberth, Sonja

AU - Eils, Roland

AU - Flicek, Paul

AU - Haas, Siegfried

AU - Hummel, Michael

AU - Karsch, Dennis

AU - Kerstens, Hinrik H.D.

AU - Klapper, Wolfram

AU - Kreuz, Markus

AU - Lawerenz, Chris

AU - Lenze, Dido

AU - Loeffler, Markus

AU - López, Cristina

AU - MacLeod, Roderick A.F.

AU - Martens, Joost H.A.

AU - Kulis, Marta

AU - Martín-Subero, José Ignacio

AU - Möller, Peter

AU - Nagel, Inga

AU - Picelli, Simone

AU - Vater, Inga

AU - Rohde, Marius

AU - Rosenstiel, Philip

AU - Rosolowski, Maciej

AU - Russell, Robert B.

AU - Schilhabel, Markus

AU - Schlesner, Matthias

AU - Stadler, Peter F.

AU - Szczepanowski, Monika

AU - Trümper, Lorenz

AU - Stunnenberg, Hendrik G.

AU - Küppers, Ralf

AU - Ammerpohl, Ole

AU - Lichter, Peter

AU - Siebert, Reiner

AU - Hoffmann, Steve

AU - Radlwimmer, Bernhard

PY - 2015/11/1

Y1 - 2015/11/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84995360059&partnerID=8YFLogxK

U2 - 10.1038/ng.3413

DO - 10.1038/ng.3413

M3 - Article

C2 - 26437030

AN - SCOPUS:84995360059

SN - 1061-4036

VL - 47

SP - 1316

EP - 1325

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -

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

Abstract

Access to Document

Fingerprint

Cite this