Molecular characterization of Richter syndrome identifies de novo diffuse large B-cell lymphomas with poor prognosis
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Published:2023-01-19
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Broséus JulienORCID, Hergalant SébastienORCID, Vogt JuliaORCID, Tausch Eugen, Kreuz Markus, Mottok Anja, Schneider Christof, Dartigeas Caroline, Roos-Weil Damien, Quinquenel Anne, Moulin Charline, Ott German, Blanchet OdileORCID, Tomowiak CécileORCID, Lazarian Grégory, Rouyer Pierre, Chteinberg Emil, Bernhart Stephan H., Tournilhac Olivier, Gauchotte Guillaume, Lomazzi Sandra, Chapiro EliseORCID, Nguyen-Khac FlorenceORCID, Chery Céline, Davi Frédéric, Hunault Mathilde, Houlgatte Rémi, Rosenwald Andreas, Delmer AlainORCID, Meyre David, Béné Marie-ChristineORCID, Thieblemont Catherine, Lichter Peter, Ammerpohl Ole, Guéant Jean-LouisORCID, Bernhart Stephan, Guièze Romain, Martin-Subero José IgnacioORCID, Cymbalista Florence, Feugier Pierre, Siebert Reiner, Stilgenbauer StephanORCID,
Abstract
AbstractRichter 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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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