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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.

SUBMITTER: Queiros AC 

PROVIDER: S-EPMC5805090 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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

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

Cancer cell 20161101 5


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  ...[more]

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