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Molecular characterization of Richter syndrome identifies de novo diffuse large B-cell lymphomas with poor prognosis

Author

Listed:
  • Julien Broséus

    (Ulm University
    Université de Lorraine
    CHRU-Nancy, Service d’Hématologie Biologique, Pôle Laboratoires)

  • Sébastien Hergalant

    (Université de Lorraine)

  • Julia Vogt

    (Ulm University & Ulm University Medical Center)

  • Eugen Tausch

    (Ulm University)

  • Markus Kreuz

    (Fraunhofer Institute for Cell Therapy and Immunology IZI)

  • Anja Mottok

    (Ulm University & Ulm University Medical Center)

  • Christof Schneider

    (Ulm University)

  • Caroline Dartigeas

    (University Hospital of Tours)

  • Damien Roos-Weil

    (Hôpital de la Pitié-Salpêtrière, AP-HP)

  • Anne Quinquenel

    (Hématologie Clinique)

  • Charline Moulin

    (University Hospital of Nancy
    Inserm, CHRU, University of Lorraine, CIC Clinical Epidemiology)

  • German Ott

    (Department of Clinical Pathology, Robert-Bosch-Krankenhaus, and Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology)

  • Odile Blanchet

    (Laboratoire d’Hématologie)

  • Cécile Tomowiak

    (CHU Poitiers
    CIC1402 Inserm Poitiers)

  • Grégory Lazarian

    (Assistance Publique-Hôpitaux de Paris)

  • Pierre Rouyer

    (Université de Lorraine)

  • Emil Chteinberg

    (Ulm University & Ulm University Medical Center)

  • Stephan H. Bernhart

    (Leipzig University)

  • Olivier Tournilhac

    (Clermont-Ferrand University Hospital)

  • Guillaume Gauchotte

    (Université de Lorraine
    BBB, CHRU Nancy)

  • Sandra Lomazzi

    (BB-0033-00035, CHRU de Nancy)

  • Elise Chapiro

    (Hôpital Pitié-Salpêtrière, AP-HP
    Université Paris Diderot)

  • Florence Nguyen-Khac

    (Hôpital Pitié-Salpêtrière, AP-HP
    Université Paris Diderot)

  • Céline Chery

    (Université de Lorraine
    CHRU of Nancy, Service de Biochimie-Biologie Moléculaire-Nutrition, Pôle Laboratoires)

  • Frédéric Davi

    (Université Paris Diderot
    AP-HP, Sorbonne University)

  • Mathilde Hunault

    (University Hospital of Angers)

  • Rémi Houlgatte

    (Université de Lorraine)

  • Andreas Rosenwald

    (University Hospital of Würzburg)

  • Alain Delmer

    (Hématologie Clinique)

  • David Meyre

    (Université de Lorraine)

  • Marie-Christine Béné

    (University Hospital of Nantes
    Inserm 1232 Centre de Recherche en Cancérologie et Immunologie Nantes Angers (CRCINA))

  • Catherine Thieblemont

    (Hôpital Saint-Louis)

  • Peter Lichter

    (German Cancer Research Center (DKFZ))

  • Ole Ammerpohl

    (Ulm University & Ulm University Medical Center)

  • Jean-Louis Guéant

    (Université de Lorraine
    CHRU of Nancy, Service de Biochimie-Biologie Moléculaire-Nutrition, Pôle Laboratoires)

  • Romain Guièze

    (Clermont-Ferrand University Hospital)

  • José Ignacio Martin-Subero

    (University of Barcelona
    Institució Catalana de Recerca i Estudis Avançats (ICREA))

  • Florence Cymbalista

    (Assistance Publique-Hôpitaux de Paris)

  • Pierre Feugier

    (Université de Lorraine
    University Hospital of Nancy)

  • Reiner Siebert

    (Ulm University & Ulm University Medical Center)

  • Stephan Stilgenbauer

    (Ulm University)

Abstract

Richter syndrome (RS) is the transformation of chronic lymphocytic leukemia (CLL) into aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL). We characterize 58 primary human RS samples by genome-wide DNA methylation and whole-transcriptome profiling. Our comprehensive approach determines RS DNA methylation profile and unravels a CLL epigenetic imprint, allowing CLL-RS clonal relationship assessment without the need of the initial CLL tumor DNA. DNA methylation- and transcriptomic-based classifiers were developed, and testing on landmark DLBCL datasets identifies a poor-prognosis, activated B-cell-like DLBCL subset in 111/1772 samples. The classification robustly identifies phenotypes very similar to RS with a specific genomic profile, accounting for 4.3-8.3% of de novo DLBCLs. In this work, RS multi-omics characterization determines oncogenic mechanisms, establishes a surrogate marker for CLL-RS clonal relationship, and provides a clinically relevant classifier for a subset of primary “RS-type DLBCL” with unfavorable prognosis.

Suggested Citation

  • Julien Broséus & Sébastien Hergalant & Julia Vogt & Eugen Tausch & Markus Kreuz & Anja Mottok & Christof Schneider & Caroline Dartigeas & Damien Roos-Weil & Anne Quinquenel & Charline Moulin & German , 2023. "Molecular characterization of Richter syndrome identifies de novo diffuse large B-cell lymphomas with poor prognosis," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-34642-6
    DOI: 10.1038/s41467-022-34642-6
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    References listed on IDEAS

    as
    1. Axel Visel & Edward M. Rubin & Len A. Pennacchio, 2009. "Genomic views of distant-acting enhancers," Nature, Nature, vol. 461(7261), pages 199-205, September.
    2. Heng Pan & Yanwen Jiang & Michela Boi & Fabrizio Tabbò & David Redmond & Kui Nie & Marco Ladetto & Annalisa Chiappella & Leandro Cerchietti & Rita Shaknovich & Ari M. Melnick & Giorgio G. Inghirami & , 2015. "Epigenomic evolution in diffuse large B-cell lymphomas," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    3. Josse, Julie & Husson, François, 2016. "missMDA: A Package for Handling Missing Values in Multivariate Data Analysis," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 70(i01).
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