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

Publication date: 14 November 2016
Source:Cancer Cell, Volume 30, Issue 5
Author(s): 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
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.

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Teaser

As part of the IHEC consortium, Queirós et al. perform an epigenomic analysis of mantle cell lymphoma, which reveals two major subtypes with distinct clinicobiological features and identifies distant enhancers as potential epigenetic drivers. Explore the Cell Press IHEC web portal http://ift.tt/2gczkgR.


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