Portal de Periódicos da CAPES

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

2016; Cell Press; Volume: 30; Issue: 5 Linguagem: Inglês

10.1016/j.ccell.2016.09.014

1878-3686

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

Cancer-related gene regulation

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.