Molecular characterization of Richter syndrome identifies de novo diffuse large B-cell lymphomas with poor prognosis
peer-reviewed
Erstveröffentlichung
2023-01-19Authors
Broseus, Julien
Hergalant, Sebastien
Vogt, Julia
Tausch, Eugen
Kreuz, Markus
Wissenschaftlicher Artikel
Published in
Nature Communications ; 14 (2023). - Art.-Nr. 309. - eISSN 2041-1723
Link to original publication
https://dx.doi.org//10.1038/s41467-022-34642-6Institutions
UKU. Klinik für Innere Medizin IIIUKU. Institut für Humangenetik
Document version
published version (publisher's PDF)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.
DFG Project THU
SFB 1074 Teilprojekt B01 / Genomische Instabilität, Krankheitsevolution und neue Behandlungsstrategien im CLL Mausmodell / DFG / 217328187
SFB 1074 Teilprojekt B09 / Ursachen und Konsequenzen der epigenetischen Veränderungen bei der T-Zell Prolymphozyten-Leukämie / DFG / 217328187
SFB 1074 Teilprojekt B09 / Ursachen und Konsequenzen der epigenetischen Veränderungen bei der T-Zell Prolymphozyten-Leukämie / DFG / 217328187
Project uulm
ICGC / Internationales Krebsgenomkonsortium (ICGC): Bestimmung der molekularen Mechanismen beim Malignen Lymphom (ICGC-MMML-Seq); Arbeitspaket WP2 / BMBF / 01KU1002D
ICGC-Data Mining / ICGC-Data Mining: Charakterisierung des nicht-Protein-kodierenden Subgenoms in Tumorzellen, Standort Ulm / BMBF / 01KU1505G
ICGC-Data Mining / ICGC-Data Mining: Charakterisierung des nicht-Protein-kodierenden Subgenoms in Tumorzellen, Standort Ulm / BMBF / 01KU1505G
Is supplemented by
https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-34642-6/MediaObjects/41467_2022_34642_MOESM1_ESM.pdfhttps://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-34642-6/MediaObjects/41467_2022_34642_MOESM2_ESM.pdf
https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-34642-6/MediaObjects/41467_2022_34642_MOESM3_ESM.pdf
https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-34642-6/MediaObjects/41467_2022_34642_MOESM4_ESM.xlsx
https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-34642-6/MediaObjects/41467_2022_34642_MOESM5_ESM.pdf
Subject headings
[GND]: B-Zell-Lymphom | Epigenetik[LCSH]: Chronic lymphocytic leukemia | Epigenetics
[MeSH]: Lymphoma, B-Cell | Computational Biology | Epigenomics | Gene Expression Profiling
[Free subject headings]: B-cell lymphoma | Computational biology and bioinformatics | Transcriptomics
[DDC subject group]: DDC 570 / Life sciences | DDC 610 / Medicine & health
Metadata
Show full item recordDOI & citation
Please use this identifier to cite or link to this item: http://dx.doi.org/10.18725/OPARU-48887
Broseus, Julien et al. (2023): Molecular characterization of Richter syndrome identifies de novo diffuse large B-cell lymphomas with poor prognosis. Open Access Repositorium der Universität Ulm und Technischen Hochschule Ulm. http://dx.doi.org/10.18725/OPARU-48887
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