Proteogenomics refines the molecular classification of chronic lymphocytic leukemia
© 2022. The Author(s)..
Cancer heterogeneity at the proteome level may explain differences in therapy response and prognosis beyond the currently established genomic and transcriptomic-based diagnostics. The relevance of proteomics for disease classifications remains to be established in clinically heterogeneous cancer entities such as chronic lymphocytic leukemia (CLL). Here, we characterize the proteome and transcriptome alongside genetic and ex-vivo drug response profiling in a clinically annotated CLL discovery cohort (n = 68). Unsupervised clustering of the proteome data reveals six subgroups. Five of these proteomic groups are associated with genetic features, while one group is only detectable at the proteome level. This new group is characterized by accelerated disease progression, high spliceosomal protein abundances associated with aberrant splicing, and low B cell receptor signaling protein abundances (ASB-CLL). Classifiers developed to identify ASB-CLL based on its characteristic proteome or splicing signature in two independent cohorts (n = 165, n = 169) confirm that ASB-CLL comprises about 20% of CLL patients. The inferior overall survival in ASB-CLL is also independent of both TP53- and IGHV mutation status. Our multi-omics analysis refines the classification of CLL and highlights the potential of proteomics to improve cancer patient stratification beyond genetic and transcriptomic profiling.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
|---|---|
| Enthalten in: |
Nature communications - 13(2022), 1 vom: 20. Okt., Seite 6226 |
| Sprache: |
Englisch |
|---|
| Links: |
|---|
| Themen: |
Journal Article |
|---|
| Anmerkungen: |
Date Completed 24.10.2022 Date Revised 22.12.2022 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41467-022-33385-8 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM347809219 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM347809219 | ||
| 003 | DE-627 | ||
| 005 | 20231226034721.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41467-022-33385-8 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1159.xml |
| 035 | |a (DE-627)NLM347809219 | ||
| 035 | |a (NLM)36266272 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Herbst, Sophie A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Proteogenomics refines the molecular classification of chronic lymphocytic leukemia |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 24.10.2022 | ||
| 500 | |a Date Revised 22.12.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s). | ||
| 520 | |a Cancer heterogeneity at the proteome level may explain differences in therapy response and prognosis beyond the currently established genomic and transcriptomic-based diagnostics. The relevance of proteomics for disease classifications remains to be established in clinically heterogeneous cancer entities such as chronic lymphocytic leukemia (CLL). Here, we characterize the proteome and transcriptome alongside genetic and ex-vivo drug response profiling in a clinically annotated CLL discovery cohort (n = 68). Unsupervised clustering of the proteome data reveals six subgroups. Five of these proteomic groups are associated with genetic features, while one group is only detectable at the proteome level. This new group is characterized by accelerated disease progression, high spliceosomal protein abundances associated with aberrant splicing, and low B cell receptor signaling protein abundances (ASB-CLL). Classifiers developed to identify ASB-CLL based on its characteristic proteome or splicing signature in two independent cohorts (n = 165, n = 169) confirm that ASB-CLL comprises about 20% of CLL patients. The inferior overall survival in ASB-CLL is also independent of both TP53- and IGHV mutation status. Our multi-omics analysis refines the classification of CLL and highlights the potential of proteomics to improve cancer patient stratification beyond genetic and transcriptomic profiling | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Proteome |2 NLM | |
| 650 | 7 | |a Receptors, Antigen, B-Cell |2 NLM | |
| 700 | 1 | |a Vesterlund, Mattias |e verfasserin |4 aut | |
| 700 | 1 | |a Helmboldt, Alexander J |e verfasserin |4 aut | |
| 700 | 1 | |a Jafari, Rozbeh |e verfasserin |4 aut | |
| 700 | 1 | |a Siavelis, Ioannis |e verfasserin |4 aut | |
| 700 | 1 | |a Stahl, Matthias |e verfasserin |4 aut | |
| 700 | 1 | |a Schitter, Eva C |e verfasserin |4 aut | |
| 700 | 1 | |a Liebers, Nora |e verfasserin |4 aut | |
| 700 | 1 | |a Brinkmann, Berit J |e verfasserin |4 aut | |
| 700 | 1 | |a Czernilofsky, Felix |e verfasserin |4 aut | |
| 700 | 1 | |a Roider, Tobias |e verfasserin |4 aut | |
| 700 | 1 | |a Bruch, Peter-Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Iskar, Murat |e verfasserin |4 aut | |
| 700 | 1 | |a Kittai, Adam |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Junyan |e verfasserin |4 aut | |
| 700 | 1 | |a Richter, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Mermelekas, Georgios |e verfasserin |4 aut | |
| 700 | 1 | |a Umer, Husen Muhammad |e verfasserin |4 aut | |
| 700 | 1 | |a Knoll, Mareike |e verfasserin |4 aut | |
| 700 | 1 | |a Kolb, Carolin |e verfasserin |4 aut | |
| 700 | 1 | |a Lenze, Angela |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Xiaofang |e verfasserin |4 aut | |
| 700 | 1 | |a Österholm, Cecilia |e verfasserin |4 aut | |
| 700 | 1 | |a Wahnschaffe, Linus |e verfasserin |4 aut | |
| 700 | 1 | |a Herling, Carmen |e verfasserin |4 aut | |
| 700 | 1 | |a Scheinost, Sebastian |e verfasserin |4 aut | |
| 700 | 1 | |a Ganzinger, Matthias |e verfasserin |4 aut | |
| 700 | 1 | |a Mansouri, Larry |e verfasserin |4 aut | |
| 700 | 1 | |a Kriegsmann, Katharina |e verfasserin |4 aut | |
| 700 | 1 | |a Kriegsmann, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Anders, Simon |e verfasserin |4 aut | |
| 700 | 1 | |a Zapatka, Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Del Poeta, Giovanni |e verfasserin |4 aut | |
| 700 | 1 | |a Zucchetto, Antonella |e verfasserin |4 aut | |
| 700 | 1 | |a Bomben, Riccardo |e verfasserin |4 aut | |
| 700 | 1 | |a Gattei, Valter |e verfasserin |4 aut | |
| 700 | 1 | |a Dreger, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Woyach, Jennifer |e verfasserin |4 aut | |
| 700 | 1 | |a Herling, Marco |e verfasserin |4 aut | |
| 700 | 1 | |a Müller-Tidow, Carsten |e verfasserin |4 aut | |
| 700 | 1 | |a Rosenquist, Richard |e verfasserin |4 aut | |
| 700 | 1 | |a Stilgenbauer, Stephan |e verfasserin |4 aut | |
| 700 | 1 | |a Zenz, Thorsten |e verfasserin |4 aut | |
| 700 | 1 | |a Huber, Wolfgang |e verfasserin |4 aut | |
| 700 | 1 | |a Tausch, Eugen |e verfasserin |4 aut | |
| 700 | 1 | |a Lehtiö, Janne |e verfasserin |4 aut | |
| 700 | 1 | |a Dietrich, Sascha |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature communications |d 2010 |g 13(2022), 1 vom: 20. Okt., Seite 6226 |w (DE-627)NLM199274525 |x 2041-1723 |7 nnns |
| 773 | 1 | 8 | |g volume:13 |g year:2022 |g number:1 |g day:20 |g month:10 |g pages:6226 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41467-022-33385-8 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 13 |j 2022 |e 1 |b 20 |c 10 |h 6226 | ||