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

Research output: Contribution to journalArticlepeer-review

96 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 languageEnglish
Pages (from-to)806-821
Number of pages16
JournalCancer Cell
Volume30
Issue number5
DOIs
Publication statusPublished - 14 Nov 2016
Externally publishedYes

Keywords

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

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