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

Fiche publication

Date publication

janvier 2023

Journal

Nature communications

Auteurs

Membres identifiés du Cancéropôle Est :
Pr FEUGIER Pierre , Pr GUEANT Jean-Louis , Dr HOULGATTE Rémy , Mme LOMAZZI Sandra , Pr BROSEUS Julien , Pr GAUCHOTTE Guillaume , Pr DELMER Alain

Tous les auteurs :
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 SH, 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 MC, Thieblemont C, Lichter P, Ammerpohl O, Guéant JL, ,Guièze R, Martin-Subero JI, Cymbalista F, Feugier P, Siebert R, Stilgenbauer S

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/36658118

Résumé

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.

Mots clés

Humans, Leukemia, Lymphocytic, Chronic, B-Cell, genetics, Lymphoma, Large B-Cell, Diffuse, genetics, B-Lymphocytes, pathology, DNA Methylation, genetics