Decoding the DNA Methylome of Mantle Cell Lymphoma in the Light of the Entire B Cell Lineage

Ana C. Queirós; Renée Beekman; Roser Vilarrasa-Blasi; Martí Duran-Ferrer; Guillem Clot; Angelika Merkel; Emanuele Raineri; Nuria Russiñol; Giancarlo Castellano; Sílvia Beà; Alba Navarro; Marta Kulis; Núria Verdaguer-Dot; Pedro Jares; Anna Enjuanes; María José Calasanz; Anke Bergmann; Inga Vater; Itziar Salaverría; Harmen J.G. van de Werken; Wyndham H. Wilson; Avik Datta; Paul Flicek; Romina Royo; Joost Martens; Eva Giné; Armando Lopez-Guillermo; Hendrik G. Stunnenberg; Wolfram Klapper; Christiane Pott; Simon Heath; Ivo G. Gut; Reiner Siebert; Elías Campo; José I. Martín-Subero

doi:10.1016/j.ccell.2016.09.014

Decoding the DNA Methylome of Mantle Cell Lymphoma in the Light of the Entire B Cell Lineage

Ana C. Queirós, Renée Beekman, Roser Vilarrasa-Blasi, Martí Duran-Ferrer, Guillem Clot, Angelika Merkel, Emanuele Raineri, Nuria Russiñol, Giancarlo Castellano, Sílvia Beà, Alba Navarro, Marta Kulis, Núria Verdaguer-Dot, Pedro Jares, Anna Enjuanes, María José Calasanz, Anke Bergmann, Inga Vater, Itziar Salaverría, Harmen J.G. van de WerkenWyndham H. Wilson, Avik Datta, Paul Flicek, Romina Royo, Joost Martens, Eva Giné, Armando Lopez-Guillermo, Hendrik G. Stunnenberg, Wolfram Klapper, Christiane Pott, Simon Heath, Ivo G. Gut, Reiner Siebert, Elías Campo, José I. Martín-Subero

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101 Citations (Scopus)

Abstract

We analyzed the in silico purified DNA methylation signatures of 82 mantle cell lymphomas (MCL) in comparison with cell subpopulations spanning the entire B cell lineage. We identified two MCL subgroups, respectively carrying epigenetic imprints of germinal-center-inexperienced and germinal-center-experienced B cells, and we found that DNA methylation profiles during lymphomagenesis are largely influenced by the methylation dynamics in normal B cells. An integrative epigenomic approach revealed 10,504 differentially methylated regions in regulatory elements marked by H3K27ac in MCL primary cases, including a distant enhancer showing de novo looping to the MCL oncogene SOX11. Finally, we observed that the magnitude of DNA methylation changes per case is highly variable and serves as an independent prognostic factor for MCL outcome.

Original language	English
Pages (from-to)	806-821
Number of pages	16
Journal	Cancer Cell
Volume	30
Issue number	5
DOIs	https://doi.org/10.1016/j.ccell.2016.09.014
Publication status	Published - 14 Nov 2016
Externally published	Yes

Keywords

ChIP-seq
chromatin
DNA looping
DNA methylation
enhancer
epigenomics
lymphoma
mantle cell lymphoma
SOX11
whole-genome bisulfite sequencing

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10.1016/j.ccell.2016.09.014

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Queirós, A. C., Beekman, R., Vilarrasa-Blasi, R., Duran-Ferrer, M., Clot, G., Merkel, A., Raineri, E., Russiñol, N., Castellano, G., Beà, S., Navarro, A., Kulis, M., Verdaguer-Dot, N., Jares, P., Enjuanes, A., Calasanz, M. J., Bergmann, A., Vater, I., Salaverría, I., ... Martín-Subero, J. I. (2016). Decoding the DNA Methylome of Mantle Cell Lymphoma in the Light of the Entire B Cell Lineage. Cancer Cell, 30(5), 806-821. https://doi.org/10.1016/j.ccell.2016.09.014

@article{f0d943927ab34b0e98356ea6481baffb,

title = "Decoding the DNA Methylome of Mantle Cell Lymphoma in the Light of the Entire B Cell Lineage",

abstract = "We analyzed the in silico purified DNA methylation signatures of 82 mantle cell lymphomas (MCL) in comparison with cell subpopulations spanning the entire B cell lineage. We identified two MCL subgroups, respectively carrying epigenetic imprints of germinal-center-inexperienced and germinal-center-experienced B cells, and we found that DNA methylation profiles during lymphomagenesis are largely influenced by the methylation dynamics in normal B cells. An integrative epigenomic approach revealed 10,504 differentially methylated regions in regulatory elements marked by H3K27ac in MCL primary cases, including a distant enhancer showing de novo looping to the MCL oncogene SOX11. Finally, we observed that the magnitude of DNA methylation changes per case is highly variable and serves as an independent prognostic factor for MCL outcome.",

keywords = "ChIP-seq, chromatin, DNA looping, DNA methylation, enhancer, epigenomics, lymphoma, mantle cell lymphoma, SOX11, whole-genome bisulfite sequencing",

author = "Queir{\'o}s, {Ana C.} and Ren{\'e}e Beekman and Roser Vilarrasa-Blasi and Mart{\'i} Duran-Ferrer and Guillem Clot and Angelika Merkel and Emanuele Raineri and Nuria Russi{\~n}ol and Giancarlo Castellano and S{\'i}lvia Be{\`a} and Alba Navarro and Marta Kulis and N{\'u}ria Verdaguer-Dot and Pedro Jares and Anna Enjuanes and Calasanz, {Mar{\'i}a Jos{\'e}} and Anke Bergmann and Inga Vater and Itziar Salaverr{\'i}a and {van de Werken}, {Harmen J.G.} and Wilson, {Wyndham H.} and Avik Datta and Paul Flicek and Romina Royo and Joost Martens and Eva Gin{\'e} and Armando Lopez-Guillermo and Stunnenberg, {Hendrik G.} and Wolfram Klapper and Christiane Pott and Simon Heath and Gut, {Ivo G.} and Reiner Siebert and El{\'i}as Campo and Mart{\'i}n-Subero, {Jos{\'e} I.}",

note = "Publisher Copyright: {\textcopyright} 2016 The Authors",

year = "2016",

month = nov,

day = "14",

doi = "10.1016/j.ccell.2016.09.014",

language = "English",

volume = "30",

pages = "806--821",

journal = "Cancer Cell",

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Queirós, AC, Beekman, R, Vilarrasa-Blasi, R, Duran-Ferrer, M, Clot, G, Merkel, A, Raineri, E, Russiñol, N, Castellano, G, Beà, S, Navarro, A, Kulis, M, Verdaguer-Dot, N, Jares, P, Enjuanes, A, Calasanz, MJ, Bergmann, A, Vater, I, Salaverría, I, van de Werken, HJG, Wilson, WH, Datta, A, Flicek, P, Royo, R, Martens, J, Giné, E, Lopez-Guillermo, A, Stunnenberg, HG, Klapper, W, Pott, C, Heath, S, Gut, IG, Siebert, R, Campo, E & Martín-Subero, JI 2016, 'Decoding the DNA Methylome of Mantle Cell Lymphoma in the Light of the Entire B Cell Lineage', Cancer Cell, vol. 30, no. 5, pp. 806-821. https://doi.org/10.1016/j.ccell.2016.09.014

TY - JOUR

T1 - Decoding the DNA Methylome of Mantle Cell Lymphoma in the Light of the Entire B Cell Lineage

AU - Queirós, Ana C.

AU - Beekman, Renée

AU - Vilarrasa-Blasi, Roser

AU - Duran-Ferrer, Martí

AU - Clot, Guillem

AU - Merkel, Angelika

AU - Raineri, Emanuele

AU - Russiñol, Nuria

AU - Castellano, Giancarlo

AU - Beà, Sílvia

AU - Navarro, Alba

AU - Kulis, Marta

AU - Verdaguer-Dot, Núria

AU - Jares, Pedro

AU - Enjuanes, Anna

AU - Calasanz, María José

AU - Bergmann, Anke

AU - Vater, Inga

AU - Salaverría, Itziar

AU - van de Werken, Harmen J.G.

AU - Wilson, Wyndham H.

AU - Datta, Avik

AU - Flicek, Paul

AU - Royo, Romina

AU - Martens, Joost

AU - Giné, Eva

AU - Lopez-Guillermo, Armando

AU - Stunnenberg, Hendrik G.

AU - Klapper, Wolfram

AU - Pott, Christiane

AU - Heath, Simon

AU - Gut, Ivo G.

AU - Siebert, Reiner

AU - Campo, Elías

AU - Martín-Subero, José I.

PY - 2016/11/14

Y1 - 2016/11/14

N2 - We analyzed the in silico purified DNA methylation signatures of 82 mantle cell lymphomas (MCL) in comparison with cell subpopulations spanning the entire B cell lineage. We identified two MCL subgroups, respectively carrying epigenetic imprints of germinal-center-inexperienced and germinal-center-experienced B cells, and we found that DNA methylation profiles during lymphomagenesis are largely influenced by the methylation dynamics in normal B cells. An integrative epigenomic approach revealed 10,504 differentially methylated regions in regulatory elements marked by H3K27ac in MCL primary cases, including a distant enhancer showing de novo looping to the MCL oncogene SOX11. Finally, we observed that the magnitude of DNA methylation changes per case is highly variable and serves as an independent prognostic factor for MCL outcome.

AB - We analyzed the in silico purified DNA methylation signatures of 82 mantle cell lymphomas (MCL) in comparison with cell subpopulations spanning the entire B cell lineage. We identified two MCL subgroups, respectively carrying epigenetic imprints of germinal-center-inexperienced and germinal-center-experienced B cells, and we found that DNA methylation profiles during lymphomagenesis are largely influenced by the methylation dynamics in normal B cells. An integrative epigenomic approach revealed 10,504 differentially methylated regions in regulatory elements marked by H3K27ac in MCL primary cases, including a distant enhancer showing de novo looping to the MCL oncogene SOX11. Finally, we observed that the magnitude of DNA methylation changes per case is highly variable and serves as an independent prognostic factor for MCL outcome.

KW - ChIP-seq

KW - chromatin

KW - DNA looping

KW - DNA methylation

KW - enhancer

KW - epigenomics

KW - lymphoma

KW - mantle cell lymphoma

KW - SOX11

KW - whole-genome bisulfite sequencing

UR - http://www.scopus.com/inward/record.url?scp=85006511752&partnerID=8YFLogxK

U2 - 10.1016/j.ccell.2016.09.014

DO - 10.1016/j.ccell.2016.09.014

M3 - Article

C2 - 27846393

AN - SCOPUS:85006511752

SN - 1535-6108

VL - 30

SP - 806

EP - 821

JO - Cancer Cell

JF - Cancer Cell

IS - 5

ER -

Decoding the DNA Methylome of Mantle Cell Lymphoma in the Light of the Entire B Cell Lineage

Abstract

Keywords

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