Journal Article

DKFZ-2023-00124

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Molecular characterization of Richter syndrome identifies de novo diffuse large B-cell lymphomas with poor prognosis.

Broséus, J. ; Hergalant, S. ; Vogt, J. ; Tausch, E. ; Kreuz, M. ; Mottok, A. ; Schneider, C. ; Dartigeas, C. ; Roos-Weil, D. ; Quinquenel, A. ; Moulin, C. ; Ott, G. ; Blanchet, O. ; Tomowiak, C. ; Lazarian, G. ; Rouyer, P. ; Chteinberg, E. ; Bernhart, S. H. ; Tournilhac, O. ; Gauchotte, G. ; Lomazzi, S. ; Chapiro, E. ; Nguyen-Khac, F. ; Chery, C. ; Davi, F. ; Hunault, M. ; Houlgatte, R. ; Rosenwald, A. ; Delmer, A. ; Meyre, D. ; Béné, M.-C. ; Thieblemont, C. ; Lichter, P.DKFZ* ; Ammerpohl, O. ; Guéant, J.-L. ; Consortium, I. M. (Collaboration Author) ; Guièze, R. ; Martin-Subero, J. I. ; Cymbalista, F. ; Feugier, P. ; Siebert, R. ; Stilgenbauer, S. ; Bernhart, S. (Contributor)

2023
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-022-34642-6

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.

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Contributing Institute(s):

1. B060 Molekulare Genetik (B060)
2. DKTK HD zentral (HD01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2023

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