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Beekman, RAuthorMerkel, AAuthorRaineri, EAuthorCastellano, GAuthorNavarro, AAuthorHeath, SAuthorGut, IgAuthor

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December 20, 2016
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Article

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

Publicated to: CANCER CELL. 30 (5): 806-821 - 2016-11-14 30(5), DOI: 10.1016/j.ccell.2016.09.014

Authors:

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
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Affiliations

BSC, Joint Program Computat Biol, Barcelona Sci Pk, Barcelona 08034, Spain - Author
Christian Albrecht Univ, Hematopathol Sect, D-24105 Kiel, Germany      University of Kiel - Author
Christian Albrecht Univ, Lymph Node Registry, D-24105 Kiel, Germany      University of Kiel - Author
Ctr Nacl Anal Genom, Parc Cient Barcelona, Barcelona 08028, Spain - Author
EBI, EMBL, Wellcome Trust Genome Campus, Hinxton CB10 1SD, England      European Molecular Biology Laboratory (EMBL)    Wellcome Trust Sanger Institute       - Author
Erasmus MC, Canc Computat Biol Ctr, NL-3015 CN Rotterdam, Netherlands      Erasmus MC Cancer Institute    Erasmus University Rotterdam    Erasmus University Medical Center - Author
Erasmus MC, Dept Cell Biol, NL-3015 CN Rotterdam, Netherlands      Erasmus University Medical Center    Erasmus University Rotterdam - Author
Erasmus MC, Dept Urol, NL-3015 CN Rotterdam, Netherlands      Erasmus University Medical Center    Erasmus University Rotterdam - Author
Hosp Clin Barcelona, Serv Anat Patol, Unidad Hematopatol, E-08036 Barcelona, Spain      Hospital Clinic de Barcelona    University of Barcelona - Author
IDIBAPS, Hosp Clin, Serv Hematol, Barcelona 08036, Spain      University of Barcelona    Hospital Clinic de Barcelona    IDIBAPS - Author
IDIBAPS, Unidad Genom, Barcelona 08036, Spain      IDIBAPS    Hospital Clinic de Barcelona    University of Barcelona - Author
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona 08036, Spain.      Hospital Clinic de Barcelona    IDIBAPS    University of Barcelona - Author
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona 08036, Spain      University of Barcelona    IDIBAPS    Hospital Clinic de Barcelona       - Author
IRB, Barcelona Sci Pk, Barcelona 08034, Spain      Barcelona Institute of Science & Technology    Institute for Research in Biomedicine - IRB Barcelona - Author
NCI, Lymphoid Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA      NIH National Cancer Institute (NCI)    National Institutes of Health (NIH) - USA - Author
Radboud Univ Nijmegen, FNWI, NCMLS, Mol Biol, NL-6500 HB Nijmegen, Netherlands      Radboud University Nijmegen - Author
Univ Barcelona, Dept Fundamentos Clin, E-08036 Barcelona, Spain.      University of Barcelona - Author
Univ Barcelona, Dept Fundamentos Clin, E-08036 Barcelona, Spain      University of Barcelona - Author
Univ Hosp Schleswig Holstein, D-24105 Kiel, Germany      Schleswig Holstein University Hospital    University of Kiel - Author
Univ Hosp Schleswig Holstein, Dept Med 2, D-24116 Kiel, Germany      University of Kiel    Schleswig Holstein University Hospital - Author
Univ Kiel, Dept Pediat, D-24105 Kiel, Germany      University of Kiel - Author
Univ Kiel, Inst Human Genet, D-24105 Kiel, Germany      University of Kiel - Author
Univ Navarra, Dept Genet, Pamplona 31008, Spain      University of Navarra - Author
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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.Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
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Keywords

chip-seqchromatindna loopingdna methylationenhancerepigenomicslymphomamantle cell lymphomasox11B-lymphocytesCancer-cellsCell line, tumorCell lineageChip-seqChromatinChronic lymphocytic-leukemiaComputer simulationDifferentiationDna loopingDna methylationEnhancerEnhancer elements, geneticEnhancersEpigenesis, geneticEpigenomeEpigenomicsGene expression regulation, neoplasticGenomeHigh-throughput nucleotide sequencingHumansLymphomaLymphoma, mantle-cellMantle cell lymphomaMethylationMolecular pathogenesisMutationsRevealsSox11Sox11 protein, humanSoxc transcription factorsWhole-genome bisulfite sequencing

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal CANCER CELL due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2016, it was in position 4/190, thus managing to position itself as a Q1 (Primer Cuartil), in the category Cell Biology.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 3.01. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 13, 2025)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 3.13 (source consulted: FECYT Mar 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2026-04-13, the following number of citations:

  • WoS: 105
  • Scopus: 109
  • Europe PMC: 61
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Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-04-13:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 197.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 197 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 52.
  • The number of mentions on the social network X (formerly Twitter): 25 (Altmetric).
  • The number of mentions on Wikipedia: 1 (Altmetric).
  • The number of mentions in news outlets: 3 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
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Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Germany; Mali; Netherlands; United Kingdom; United States of America.

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Awards linked to the item

This work was funded by the European Union's Seventh Framework Program through the Blueprint Consortium (grant agreement 282510), the European Hematology Association (Non-Clinical Advanced Research Fellowships to J.I.M.-S.), the Worldwide Cancer Research (grant number 16-1285, to J.I.M.-S.), Spanish Ministerio de Economia y Competitividad (MINECO), grant no. SAF2015-64885-R (to E.C.) and Generalitat de Catalunya Suport Grups de Recerca AGAUR 2014-SGR-795 (to E.C.). Methylation microarrays were out-sourced to the Spanish Centro Nacional de Genotipado (CEGEN-ISCIII). We are indebted to the Genomics core facility of the Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS) for technical help. This work was partially developed at the Centro Esther Koplowitz (CEK; Barcelona, Spain). J.I.M.-S. is a Ramon y Cajal researcher of MINECO, E.C. is an Academia Researcher of the "Institucio Catalana de Recerca i Estudis Avancats" (ICREA) of the Generalitat de Catalunya, A.C.Q. is supported by a Portuguese Fundacao para a Ciencia e a Tecnologia (FCT) fellowship, R.B. by fellowships from the Netherlands Organisation for Scientific Research (NWO) and the EU (Marie Curie), and R.V.-B by a pre-doctoral fellowship of the MINECO. Paul Flicek is a member of the Scientific Advisory Board for Omicia, Inc.
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