Herbst, Sophie A., Vesterlund, Mattias ORCID: 0000-0001-9471-6592, Helmboldt, Alexander J. ORCID: 0000-0002-0807-7518, Jafari, Rozbeh ORCID: 0000-0002-3396-4709, Siavelis, Ioannis, Stahl, Matthias, Schitter, Eva C., Liebers, Nora, Brinkmann, Berit J., Czernilofsky, Felix, Roider, Tobias, Bruch, Peter-Martin, Iskar, Murat ORCID: 0000-0001-8603-4313, Kittai, Adam, Huang, Ying, Lu, Junyan ORCID: 0000-0002-9211-0746, Richter, Sarah, Mermelekas, Georgios, Umer, Husen Muhammad, Knoll, Mareike, Kolb, Carolin, Lenze, Angela, Cao, Xiaofang, Osterholm, Cecilia, Wahnschaffe, Linus, Herling, Carmen, Scheinost, Sebastian, Ganzinger, Matthias, Mansouri, Larry, Kriegsmann, Katharina, Kriegsmann, Mark, Anders, Simon ORCID: 0000-0003-4868-1805, Zapatka, Marc, Del Poeta, Giovanni, Zucchetto, Antonella, Bomben, Riccardo, Gattei, Valter, Dreger, Peter, Woyach, Jennifer, Herling, Marco, Muller-Tidow, Carsten, Rosenquist, Richard ORCID: 0000-0002-0211-8788, Stilgenbauer, Stephan, Zenz, Thorsten, Huber, Wolfgang, Tausch, Eugen, Lehtioe, Janne and Dietrich, Sascha (2022). Proteogenomics refines the molecular classification of chronic lymphocytic leukemia. Nat. Commun., 13 (1). BERLIN: NATURE PORTFOLIO. ISSN 2041-1723

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Abstract

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. Proteomics can be used to refine cancer classification. Here, the authors characterise chronic lymphocytic leukaemia patients by proteogenomics, and identified a subtype of patients with poor prognosis associated with aberrant B cell receptor signalling.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Herbst, Sophie A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vesterlund, MattiasUNSPECIFIEDorcid.org/0000-0001-9471-6592UNSPECIFIED
Helmboldt, Alexander J.UNSPECIFIEDorcid.org/0000-0002-0807-7518UNSPECIFIED
Jafari, RozbehUNSPECIFIEDorcid.org/0000-0002-3396-4709UNSPECIFIED
Siavelis, IoannisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stahl, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schitter, Eva C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liebers, NoraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brinkmann, Berit J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Czernilofsky, FelixUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roider, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruch, Peter-MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Iskar, MuratUNSPECIFIEDorcid.org/0000-0001-8603-4313UNSPECIFIED
Kittai, AdamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huang, YingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lu, JunyanUNSPECIFIEDorcid.org/0000-0002-9211-0746UNSPECIFIED
Richter, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mermelekas, GeorgiosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Umer, Husen MuhammadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knoll, MareikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kolb, CarolinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lenze, AngelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cao, XiaofangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Osterholm, CeciliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wahnschaffe, LinusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herling, CarmenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scheinost, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ganzinger, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mansouri, LarryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kriegsmann, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kriegsmann, MarkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Anders, SimonUNSPECIFIEDorcid.org/0000-0003-4868-1805UNSPECIFIED
Zapatka, MarcUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Del Poeta, GiovanniUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zucchetto, AntonellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bomben, RiccardoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gattei, ValterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dreger, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Woyach, JenniferUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herling, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muller-Tidow, CarstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosenquist, RichardUNSPECIFIEDorcid.org/0000-0002-0211-8788UNSPECIFIED
Stilgenbauer, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zenz, ThorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huber, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tausch, EugenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lehtioe, JanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dietrich, SaschaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-694852
DOI: 10.1038/s41467-022-33385-8
Journal or Publication Title: Nat. Commun.
Volume: 13
Number: 1
Date: 2022
Publisher: NATURE PORTFOLIO
Place of Publication: BERLIN
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PROTEOMICS; MUTATIONS; SUBGROUPS; PROGRESSION; LANDSCAPE; SIGNATURE; SURVIVAL; GENES; TOOL; CLLMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69485

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