Proteogenomics refines the molecular classification of chronic lymphocytic leukemia
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 ent...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Herbst, Sophie - 1990- [verfasserIn] Vesterlund, Mattias [verfasserIn] Helmboldt, Alexander [verfasserIn] Jafari, Rozbeh [verfasserIn] Siavelis, Ioannis [verfasserIn] Stahl, Matthias [verfasserIn] Schitter, Eva C. - 1994- [verfasserIn] Liebers, Nora - 1989- [verfasserIn] Brinkmann, Berit J. - 1993- [verfasserIn] Czernilofsky, Felix [verfasserIn] Roider, Tobias - 1988- [verfasserIn] Bruch, Peter-Martin - 1993- [verfasserIn] Iskar, Murat [verfasserIn] Kittai, Adam [verfasserIn] Huang, Ying [verfasserIn] Lu, Junyan [verfasserIn] Richter, Sarah [verfasserIn] Mermelekas, Georgios [verfasserIn] Umer, Husen Muhammad [verfasserIn] Knoll, Mareike [verfasserIn] Kolb, Carolin [verfasserIn] Lenze, Angela [verfasserIn] Cao, Xiaofang [verfasserIn] Österholm, Cecilia [verfasserIn] Wahnschaffe, Linus [verfasserIn] Herling, Carmen [verfasserIn] Scheinost, Sebastian [verfasserIn] Ganzinger, Matthias - 1974- [verfasserIn] Mansouri, Larry [verfasserIn] Kriegsmann, Katharina - 1986- [verfasserIn] Kriegsmann, Mark - 1987- [verfasserIn] Anders, Simon [verfasserIn] Zapatka, Marc - 1974- [verfasserIn] Del Poeta, Giovanni [verfasserIn] Zucchetto, Antonella [verfasserIn] Bomben, Riccardo [verfasserIn] Gattei, Valter [verfasserIn] Dreger, Peter [verfasserIn] Woyach, Jennifer [verfasserIn] Herling, Marco [verfasserIn] Müller-Tidow, Carsten [verfasserIn] Rosenquist, Richard [verfasserIn] Stilgenbauer, Stephan [verfasserIn] Zenz, Thorsten - 1970- [verfasserIn] Huber, Wolfgang [verfasserIn] Tausch, Eugen [verfasserIn] Lehtiö, Janne [verfasserIn] Dietrich, Sascha - 1979- [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
20 October 2022 |
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| Schlagwörter: |
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| Anmerkung: |
Gesehen am 25.01.2023 |
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| Umfang: |
18 |
| Übergeordnetes Werk: |
Enthalten in: Nature Communications - [London] : Springer Nature, 2010, 13(2022) vom: Okt., Artikel-ID 6226, Seite 1-18 |
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| Übergeordnetes Werk: |
volume:13 ; year:2022 ; month:10 ; elocationid:6226 ; pages:1-18 ; extent:18 |
| Links: |
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| DOI / URN: |
10.1038/s41467-022-33385-8 |
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| Katalog-ID: |
1832441687 |
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| 245 | 1 | 0 | |a Proteogenomics refines the molecular classification of chronic lymphocytic leukemia |c Sophie A. Herbst, Mattias Vesterlund, Alexander J. Helmboldt, Rozbeh Jafari, Ioannis Siavelis, Matthias Stahl, Eva C. Schitter, Nora Liebers, Berit J. Brinkmann, Felix Czernilofsky, Tobias Roider, Peter-Martin Bruch, Murat Iskar, Adam Kittai, Ying Huang, Junyan Lu, Sarah Richter, Georgios Mermelekas, Husen Muhammad Umer, Mareike Knoll, Carolin Kolb, Angela Lenze, Xiaofang Cao, Cecilia Österholm, Linus Wahnschaffe, Carmen Herling, Sebastian Scheinost, Matthias Ganzinger, Larry Mansouri, Katharina Kriegsmann, Mark Kriegsmann, Simon Anders, Marc Zapatka, Giovanni Del Poeta, Antonella Zucchetto, Riccardo Bomben, Valter Gattei, Peter Dreger, Jennifer Woyach, Marco Herling, Carsten Müller-Tidow, Richard Rosenquist, Stephan Stilgenbauer, Thorsten Zenz, Wolfgang Huber, Eugen Tausch, Janne Lehtiö, Sascha Dietrich |
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| 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 Chronic lymphocytic leukaemia | |
| 650 | 4 | |a Computational models | |
| 650 | 4 | |a Proteomic analysis | |
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10.1038/s41467-022-33385-8 doi (DE-627)1832441687 (DE-599)KXP1832441687 (OCoLC)1389536026 DE-627 ger DE-627 rda eng Herbst, Sophie 1990- verfasserin (DE-588)115041216X (DE-627)1010727222 (DE-576)497048604 aut Proteogenomics refines the molecular classification of chronic lymphocytic leukemia Sophie A. Herbst, Mattias Vesterlund, Alexander J. Helmboldt, Rozbeh Jafari, Ioannis Siavelis, Matthias Stahl, Eva C. Schitter, Nora Liebers, Berit J. Brinkmann, Felix Czernilofsky, Tobias Roider, Peter-Martin Bruch, Murat Iskar, Adam Kittai, Ying Huang, Junyan Lu, Sarah Richter, Georgios Mermelekas, Husen Muhammad Umer, Mareike Knoll, Carolin Kolb, Angela Lenze, Xiaofang Cao, Cecilia Österholm, Linus Wahnschaffe, Carmen Herling, Sebastian Scheinost, Matthias Ganzinger, Larry Mansouri, Katharina Kriegsmann, Mark Kriegsmann, Simon Anders, Marc Zapatka, Giovanni Del Poeta, Antonella Zucchetto, Riccardo Bomben, Valter Gattei, Peter Dreger, Jennifer Woyach, Marco Herling, Carsten Müller-Tidow, Richard Rosenquist, Stephan Stilgenbauer, Thorsten Zenz, Wolfgang Huber, Eugen Tausch, Janne Lehtiö, Sascha Dietrich 20 October 2022 18 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 25.01.2023 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. Chronic lymphocytic leukaemia Computational models Proteomic analysis Vesterlund, Mattias verfasserin aut Helmboldt, Alexander verfasserin aut Jafari, Rozbeh verfasserin aut Siavelis, Ioannis verfasserin aut Stahl, Matthias verfasserin aut Schitter, Eva C. 1994- verfasserin (DE-588)1323489495 (DE-627)1883461227 aut Liebers, Nora 1989- verfasserin (DE-588)1123162875 (DE-627)879999578 (DE-576)481643850 aut Brinkmann, Berit J. 1993- verfasserin (DE-588)124968384X (DE-627)1786214849 aut Czernilofsky, Felix verfasserin (DE-588)1246918250 (DE-627)1780154399 aut Roider, Tobias 1988- verfasserin (DE-588)112919017X (DE-627)883826232 (DE-576)486252264 aut Bruch, Peter-Martin 1993- verfasserin (DE-588)1203140363 (DE-627)168794198X aut Iskar, Murat verfasserin aut Kittai, Adam verfasserin aut Huang, Ying verfasserin aut Lu, Junyan verfasserin (DE-588)124416478X (DE-627)1775109585 aut Richter, Sarah verfasserin (DE-588)1279135522 (DE-627)1832443124 aut Mermelekas, Georgios verfasserin aut Umer, Husen Muhammad verfasserin aut Knoll, Mareike verfasserin (DE-588)1279136073 (DE-627)183244323X aut Kolb, Carolin verfasserin (DE-588)1325175609 (DE-627)1884945163 aut Lenze, Angela verfasserin (DE-588)1279136545 (DE-627)1832443442 aut Cao, Xiaofang verfasserin aut Österholm, Cecilia verfasserin aut Wahnschaffe, Linus verfasserin aut Herling, Carmen verfasserin aut Scheinost, Sebastian verfasserin (DE-588)1203319711 (DE-627)168814305X aut Ganzinger, Matthias 1974- verfasserin (DE-588)102301890X (DE-627)717346471 (DE-576)366268082 aut Mansouri, Larry verfasserin aut Kriegsmann, Katharina 1986- verfasserin (DE-588)1049422449 (DE-627)781924006 (DE-576)40339774X aut Kriegsmann, Mark 1987- verfasserin (DE-588)103740324X (DE-627)755668782 (DE-576)39141870X aut Anders, Simon verfasserin (DE-588)1184492964 (DE-627)1663597936 aut Zapatka, Marc 1974- verfasserin (DE-588)128629975 (DE-627)376935782 (DE-576)297249320 aut Del Poeta, Giovanni verfasserin aut Zucchetto, Antonella verfasserin aut Bomben, Riccardo verfasserin aut Gattei, Valter verfasserin aut Dreger, Peter verfasserin (DE-588)1028891881 (DE-627)732699894 (DE-576)376320966 aut Woyach, Jennifer verfasserin aut Herling, Marco verfasserin aut Müller-Tidow, Carsten verfasserin (DE-588)1015101798 (DE-627)705330230 (DE-576)351197893 aut Rosenquist, Richard verfasserin aut Stilgenbauer, Stephan verfasserin aut Zenz, Thorsten 1970- verfasserin (DE-588)114963738 (DE-627)577184202 (DE-576)180278266 aut Huber, Wolfgang verfasserin (DE-588)1115277685 (DE-627)870097997 (DE-576)477724442 aut Tausch, Eugen verfasserin aut Lehtiö, Janne verfasserin aut Dietrich, Sascha 1979- verfasserin (DE-588)136406300 (DE-627)694354635 (DE-576)301003408 aut Enthalten in Nature Communications [London] : Springer Nature, 2010 13(2022) vom: Okt., Artikel-ID 6226, Seite 1-18 Online-Ressource (DE-627)626457688 (DE-600)2553671-0 (DE-576)331555905 2041-1723 nnns volume:13 year:2022 month:10 elocationid:6226 pages:1-18 extent:18 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10.1038/s41467-022-33385-8 doi (DE-627)1832441687 (DE-599)KXP1832441687 (OCoLC)1389536026 DE-627 ger DE-627 rda eng Herbst, Sophie 1990- verfasserin (DE-588)115041216X (DE-627)1010727222 (DE-576)497048604 aut Proteogenomics refines the molecular classification of chronic lymphocytic leukemia Sophie A. Herbst, Mattias Vesterlund, Alexander J. Helmboldt, Rozbeh Jafari, Ioannis Siavelis, Matthias Stahl, Eva C. Schitter, Nora Liebers, Berit J. Brinkmann, Felix Czernilofsky, Tobias Roider, Peter-Martin Bruch, Murat Iskar, Adam Kittai, Ying Huang, Junyan Lu, Sarah Richter, Georgios Mermelekas, Husen Muhammad Umer, Mareike Knoll, Carolin Kolb, Angela Lenze, Xiaofang Cao, Cecilia Österholm, Linus Wahnschaffe, Carmen Herling, Sebastian Scheinost, Matthias Ganzinger, Larry Mansouri, Katharina Kriegsmann, Mark Kriegsmann, Simon Anders, Marc Zapatka, Giovanni Del Poeta, Antonella Zucchetto, Riccardo Bomben, Valter Gattei, Peter Dreger, Jennifer Woyach, Marco Herling, Carsten Müller-Tidow, Richard Rosenquist, Stephan Stilgenbauer, Thorsten Zenz, Wolfgang Huber, Eugen Tausch, Janne Lehtiö, Sascha Dietrich 20 October 2022 18 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 25.01.2023 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. Chronic lymphocytic leukaemia Computational models Proteomic analysis Vesterlund, Mattias verfasserin aut Helmboldt, Alexander verfasserin aut Jafari, Rozbeh verfasserin aut Siavelis, Ioannis verfasserin aut Stahl, Matthias verfasserin aut Schitter, Eva C. 1994- verfasserin (DE-588)1323489495 (DE-627)1883461227 aut Liebers, Nora 1989- verfasserin (DE-588)1123162875 (DE-627)879999578 (DE-576)481643850 aut Brinkmann, Berit J. 1993- verfasserin (DE-588)124968384X (DE-627)1786214849 aut Czernilofsky, Felix verfasserin (DE-588)1246918250 (DE-627)1780154399 aut Roider, Tobias 1988- verfasserin (DE-588)112919017X (DE-627)883826232 (DE-576)486252264 aut Bruch, Peter-Martin 1993- verfasserin (DE-588)1203140363 (DE-627)168794198X aut Iskar, Murat verfasserin aut Kittai, Adam verfasserin aut Huang, Ying verfasserin aut Lu, Junyan verfasserin (DE-588)124416478X (DE-627)1775109585 aut Richter, Sarah verfasserin (DE-588)1279135522 (DE-627)1832443124 aut Mermelekas, Georgios verfasserin aut Umer, Husen Muhammad verfasserin aut Knoll, Mareike verfasserin (DE-588)1279136073 (DE-627)183244323X aut Kolb, Carolin verfasserin (DE-588)1325175609 (DE-627)1884945163 aut Lenze, Angela verfasserin (DE-588)1279136545 (DE-627)1832443442 aut Cao, Xiaofang verfasserin aut Österholm, Cecilia verfasserin aut Wahnschaffe, Linus verfasserin aut Herling, Carmen verfasserin aut Scheinost, Sebastian verfasserin (DE-588)1203319711 (DE-627)168814305X aut Ganzinger, Matthias 1974- verfasserin (DE-588)102301890X (DE-627)717346471 (DE-576)366268082 aut Mansouri, Larry verfasserin aut Kriegsmann, Katharina 1986- verfasserin (DE-588)1049422449 (DE-627)781924006 (DE-576)40339774X aut Kriegsmann, Mark 1987- verfasserin (DE-588)103740324X (DE-627)755668782 (DE-576)39141870X aut Anders, Simon verfasserin (DE-588)1184492964 (DE-627)1663597936 aut Zapatka, Marc 1974- verfasserin (DE-588)128629975 (DE-627)376935782 (DE-576)297249320 aut Del Poeta, Giovanni verfasserin aut Zucchetto, Antonella verfasserin aut Bomben, Riccardo verfasserin aut Gattei, Valter verfasserin aut Dreger, Peter verfasserin (DE-588)1028891881 (DE-627)732699894 (DE-576)376320966 aut Woyach, Jennifer verfasserin aut Herling, Marco verfasserin aut Müller-Tidow, Carsten verfasserin (DE-588)1015101798 (DE-627)705330230 (DE-576)351197893 aut Rosenquist, Richard verfasserin aut Stilgenbauer, Stephan verfasserin aut Zenz, Thorsten 1970- verfasserin (DE-588)114963738 (DE-627)577184202 (DE-576)180278266 aut Huber, Wolfgang verfasserin (DE-588)1115277685 (DE-627)870097997 (DE-576)477724442 aut Tausch, Eugen verfasserin aut Lehtiö, Janne verfasserin aut Dietrich, Sascha 1979- verfasserin (DE-588)136406300 (DE-627)694354635 (DE-576)301003408 aut Enthalten in Nature Communications [London] : Springer Nature, 2010 13(2022) vom: Okt., Artikel-ID 6226, Seite 1-18 Online-Ressource (DE-627)626457688 (DE-600)2553671-0 (DE-576)331555905 2041-1723 nnns volume:13 year:2022 month:10 elocationid:6226 pages:1-18 extent:18 https://doi.org/10.1038/s41467-022-33385-8 Verlag Resolving-System kostenfrei Volltext https://www.nature.com/articles/s41467-022-33385-8 Verlag kostenfrei Volltext GBV_USEFLAG_U GBV_ILN_2011 ISIL_DE-16 SYSFLAG_1 GBV_KXP SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2110 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 GBV_ILN_2013 GBV_ILN_2403 GBV_ILN_2013 ISIL_DE-16-250 GBV_ILN_2403 ISIL_DE-LFER AR 13 2022 10 6226 1-18 18 2011 01 DE-16 4455970592 00 --%%-- --%%-- --%%-- --%%-- l01 12-01-24 2013 01 DE-16-250 4251589254 00 --%%-- --%%-- --%%-- --%%-- l01 25-01-23 2013 02 DE-16-250 425159598X 00 --%%-- --%%-- --%%-- --%%-- l02 25-01-23 2403 01 DE-LFER 4476333125 00 --%%-- --%%-- n --%%-- l01 05-02-24 2403 01 DE-LFER https://doi.org/10.1038/s41467-022-33385-8 2403 01 DE-LFER https://www.nature.com/articles/s41467-022-33385-8 2013 01 DE-16-250 00 s hd2022 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_48 2013 01 DE-16-250 03 s s_18 2013 01 DE-16-250 04 p (DE-627)1567052428 Herbst, Sophie 2013 01 DE-16-250 04 k (DE-627)1416822720 Extern 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_1 2013 01 DE-16-250 05 p (DE-627)1551644037 Liebers, Nora 2013 01 DE-16-250 05 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_8 2013 01 DE-16-250 06 p (DE-627)1786214857 Brinkmann, Berit J. 2013 01 DE-16-250 06 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 06 s pos_9 2013 01 DE-16-250 07 p (DE-627)1780154534 Czernilofsky, Felix 2013 01 DE-16-250 07 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 07 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 07 s pos_10 2013 01 DE-16-250 08 p (DE-627)1571891331 Roider, Tobias 2013 01 DE-16-250 08 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 08 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 08 s pos_11 2013 01 DE-16-250 09 p (DE-627)1687959978 Bruch, Peter-Martin 2013 01 DE-16-250 09 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 09 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 09 s pos_12 2013 01 DE-16-250 10 p (DE-627)1775109623 Lu, Junyan 2013 01 DE-16-250 10 k (DE-627)1495544966 Zentrum für Infektiologie 2013 01 DE-16-250 10 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 10 s pos_16 2013 01 DE-16-250 11 p (DE-627)1832443132 Richter, Sarah 2013 01 DE-16-250 11 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 11 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 11 s pos_17 2013 01 DE-16-250 12 p (DE-627)1832443256 Knoll, Mareike 2013 01 DE-16-250 12 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 12 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 12 s pos_20 2013 01 DE-16-250 13 p (DE-627)1884945511 Kolb, Carolin 2013 01 DE-16-250 13 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 13 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 13 s pos_21 2013 01 DE-16-250 14 p (DE-627)1832443469 Lenze, Angela 2013 01 DE-16-250 14 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 14 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 14 s pos_22 2013 01 DE-16-250 15 p (DE-627)1492819603 Ganzinger, Matthias 2013 01 DE-16-250 15 k (DE-627)1888973080 Institut für Medizinische Informatik 2013 01 DE-16-250 15 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 15 s pos_28 2013 01 DE-16-250 16 p (DE-627)1576519953 Kriegsmann, Katharina 2013 01 DE-16-250 16 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 16 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 16 s pos_30 2013 01 DE-16-250 17 p (DE-627)1480997641 Kriegsmann, Mark 2013 01 DE-16-250 17 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 17 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 17 s pos_31 2013 01 DE-16-250 18 p (DE-627)1663598371 Anders, Simon 2013 01 DE-16-250 18 k (DE-627)1416734031 BIOQUANT 2013 01 DE-16-250 18 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 18 s pos_32 2013 01 DE-16-250 19 p (DE-627)1550450158 Zapatka, Marc 2013 01 DE-16-250 19 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 19 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 19 s pos_33 2013 02 DE-16-250 00 s hd2022 2013 02 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 02 DE-16-250 02 s per_48 2013 02 DE-16-250 03 s s_18 2013 02 DE-16-250 04 p (DE-627)1447864395 Dreger, Peter 2013 02 DE-16-250 04 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 02 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 02 DE-16-250 04 s pos_38 2013 02 DE-16-250 05 p (DE-627)1571744517 Müller-Tidow, Carsten 2013 02 DE-16-250 05 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 02 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 02 DE-16-250 05 s pos_41 2013 02 DE-16-250 06 p (DE-627)1504263316 Dietrich, Sascha 2013 02 DE-16-250 06 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 02 DE-16-250 06 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 02 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 02 DE-16-250 06 s pos_48 |
| allfields_unstemmed |
10.1038/s41467-022-33385-8 doi (DE-627)1832441687 (DE-599)KXP1832441687 (OCoLC)1389536026 DE-627 ger DE-627 rda eng Herbst, Sophie 1990- verfasserin (DE-588)115041216X (DE-627)1010727222 (DE-576)497048604 aut Proteogenomics refines the molecular classification of chronic lymphocytic leukemia Sophie A. Herbst, Mattias Vesterlund, Alexander J. Helmboldt, Rozbeh Jafari, Ioannis Siavelis, Matthias Stahl, Eva C. Schitter, Nora Liebers, Berit J. Brinkmann, Felix Czernilofsky, Tobias Roider, Peter-Martin Bruch, Murat Iskar, Adam Kittai, Ying Huang, Junyan Lu, Sarah Richter, Georgios Mermelekas, Husen Muhammad Umer, Mareike Knoll, Carolin Kolb, Angela Lenze, Xiaofang Cao, Cecilia Österholm, Linus Wahnschaffe, Carmen Herling, Sebastian Scheinost, Matthias Ganzinger, Larry Mansouri, Katharina Kriegsmann, Mark Kriegsmann, Simon Anders, Marc Zapatka, Giovanni Del Poeta, Antonella Zucchetto, Riccardo Bomben, Valter Gattei, Peter Dreger, Jennifer Woyach, Marco Herling, Carsten Müller-Tidow, Richard Rosenquist, Stephan Stilgenbauer, Thorsten Zenz, Wolfgang Huber, Eugen Tausch, Janne Lehtiö, Sascha Dietrich 20 October 2022 18 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 25.01.2023 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. Chronic lymphocytic leukaemia Computational models Proteomic analysis Vesterlund, Mattias verfasserin aut Helmboldt, Alexander verfasserin aut Jafari, Rozbeh verfasserin aut Siavelis, Ioannis verfasserin aut Stahl, Matthias verfasserin aut Schitter, Eva C. 1994- verfasserin (DE-588)1323489495 (DE-627)1883461227 aut Liebers, Nora 1989- verfasserin (DE-588)1123162875 (DE-627)879999578 (DE-576)481643850 aut Brinkmann, Berit J. 1993- verfasserin (DE-588)124968384X (DE-627)1786214849 aut Czernilofsky, Felix verfasserin (DE-588)1246918250 (DE-627)1780154399 aut Roider, Tobias 1988- verfasserin (DE-588)112919017X (DE-627)883826232 (DE-576)486252264 aut Bruch, Peter-Martin 1993- verfasserin (DE-588)1203140363 (DE-627)168794198X aut Iskar, Murat verfasserin aut Kittai, Adam verfasserin aut Huang, Ying verfasserin aut Lu, Junyan verfasserin (DE-588)124416478X (DE-627)1775109585 aut Richter, Sarah verfasserin (DE-588)1279135522 (DE-627)1832443124 aut Mermelekas, Georgios verfasserin aut Umer, Husen Muhammad verfasserin aut Knoll, Mareike verfasserin (DE-588)1279136073 (DE-627)183244323X aut Kolb, Carolin verfasserin (DE-588)1325175609 (DE-627)1884945163 aut Lenze, Angela verfasserin (DE-588)1279136545 (DE-627)1832443442 aut Cao, Xiaofang verfasserin aut Österholm, Cecilia verfasserin aut Wahnschaffe, Linus verfasserin aut Herling, Carmen verfasserin aut Scheinost, Sebastian verfasserin (DE-588)1203319711 (DE-627)168814305X aut Ganzinger, Matthias 1974- verfasserin (DE-588)102301890X (DE-627)717346471 (DE-576)366268082 aut Mansouri, Larry verfasserin aut Kriegsmann, Katharina 1986- verfasserin (DE-588)1049422449 (DE-627)781924006 (DE-576)40339774X aut Kriegsmann, Mark 1987- verfasserin (DE-588)103740324X (DE-627)755668782 (DE-576)39141870X aut Anders, Simon verfasserin (DE-588)1184492964 (DE-627)1663597936 aut Zapatka, Marc 1974- verfasserin (DE-588)128629975 (DE-627)376935782 (DE-576)297249320 aut Del Poeta, Giovanni verfasserin aut Zucchetto, Antonella verfasserin aut Bomben, Riccardo verfasserin aut Gattei, Valter verfasserin aut Dreger, Peter verfasserin (DE-588)1028891881 (DE-627)732699894 (DE-576)376320966 aut Woyach, Jennifer verfasserin aut Herling, Marco verfasserin aut Müller-Tidow, Carsten verfasserin (DE-588)1015101798 (DE-627)705330230 (DE-576)351197893 aut Rosenquist, Richard verfasserin aut Stilgenbauer, Stephan verfasserin aut Zenz, Thorsten 1970- verfasserin (DE-588)114963738 (DE-627)577184202 (DE-576)180278266 aut Huber, Wolfgang verfasserin (DE-588)1115277685 (DE-627)870097997 (DE-576)477724442 aut Tausch, Eugen verfasserin aut Lehtiö, Janne verfasserin aut Dietrich, Sascha 1979- verfasserin (DE-588)136406300 (DE-627)694354635 (DE-576)301003408 aut Enthalten in Nature Communications [London] : Springer Nature, 2010 13(2022) vom: Okt., Artikel-ID 6226, Seite 1-18 Online-Ressource (DE-627)626457688 (DE-600)2553671-0 (DE-576)331555905 2041-1723 nnns volume:13 year:2022 month:10 elocationid:6226 pages:1-18 extent:18 https://doi.org/10.1038/s41467-022-33385-8 Verlag Resolving-System kostenfrei Volltext https://www.nature.com/articles/s41467-022-33385-8 Verlag kostenfrei Volltext GBV_USEFLAG_U GBV_ILN_2011 ISIL_DE-16 SYSFLAG_1 GBV_KXP SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2110 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 GBV_ILN_2013 GBV_ILN_2403 GBV_ILN_2013 ISIL_DE-16-250 GBV_ILN_2403 ISIL_DE-LFER AR 13 2022 10 6226 1-18 18 2011 01 DE-16 4455970592 00 --%%-- --%%-- --%%-- --%%-- l01 12-01-24 2013 01 DE-16-250 4251589254 00 --%%-- --%%-- --%%-- --%%-- l01 25-01-23 2013 02 DE-16-250 425159598X 00 --%%-- --%%-- --%%-- --%%-- l02 25-01-23 2403 01 DE-LFER 4476333125 00 --%%-- --%%-- n --%%-- l01 05-02-24 2403 01 DE-LFER https://doi.org/10.1038/s41467-022-33385-8 2403 01 DE-LFER https://www.nature.com/articles/s41467-022-33385-8 2013 01 DE-16-250 00 s hd2022 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_48 2013 01 DE-16-250 03 s s_18 2013 01 DE-16-250 04 p (DE-627)1567052428 Herbst, Sophie 2013 01 DE-16-250 04 k (DE-627)1416822720 Extern 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_1 2013 01 DE-16-250 05 p (DE-627)1551644037 Liebers, Nora 2013 01 DE-16-250 05 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_8 2013 01 DE-16-250 06 p (DE-627)1786214857 Brinkmann, Berit J. 2013 01 DE-16-250 06 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 06 s pos_9 2013 01 DE-16-250 07 p (DE-627)1780154534 Czernilofsky, Felix 2013 01 DE-16-250 07 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 07 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 07 s pos_10 2013 01 DE-16-250 08 p (DE-627)1571891331 Roider, Tobias 2013 01 DE-16-250 08 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 08 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 08 s pos_11 2013 01 DE-16-250 09 p (DE-627)1687959978 Bruch, Peter-Martin 2013 01 DE-16-250 09 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 09 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 09 s pos_12 2013 01 DE-16-250 10 p (DE-627)1775109623 Lu, Junyan 2013 01 DE-16-250 10 k (DE-627)1495544966 Zentrum für Infektiologie 2013 01 DE-16-250 10 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 10 s pos_16 2013 01 DE-16-250 11 p (DE-627)1832443132 Richter, Sarah 2013 01 DE-16-250 11 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 11 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 11 s pos_17 2013 01 DE-16-250 12 p (DE-627)1832443256 Knoll, Mareike 2013 01 DE-16-250 12 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 12 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 12 s pos_20 2013 01 DE-16-250 13 p (DE-627)1884945511 Kolb, Carolin 2013 01 DE-16-250 13 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 13 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 13 s pos_21 2013 01 DE-16-250 14 p (DE-627)1832443469 Lenze, Angela 2013 01 DE-16-250 14 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 14 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 14 s pos_22 2013 01 DE-16-250 15 p (DE-627)1492819603 Ganzinger, Matthias 2013 01 DE-16-250 15 k (DE-627)1888973080 Institut für Medizinische Informatik 2013 01 DE-16-250 15 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 15 s pos_28 2013 01 DE-16-250 16 p (DE-627)1576519953 Kriegsmann, Katharina 2013 01 DE-16-250 16 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 16 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 16 s pos_30 2013 01 DE-16-250 17 p (DE-627)1480997641 Kriegsmann, Mark 2013 01 DE-16-250 17 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 17 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 17 s pos_31 2013 01 DE-16-250 18 p (DE-627)1663598371 Anders, Simon 2013 01 DE-16-250 18 k (DE-627)1416734031 BIOQUANT 2013 01 DE-16-250 18 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 18 s pos_32 2013 01 DE-16-250 19 p (DE-627)1550450158 Zapatka, Marc 2013 01 DE-16-250 19 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 19 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 19 s pos_33 2013 02 DE-16-250 00 s hd2022 2013 02 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 02 DE-16-250 02 s per_48 2013 02 DE-16-250 03 s s_18 2013 02 DE-16-250 04 p (DE-627)1447864395 Dreger, Peter 2013 02 DE-16-250 04 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 02 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 02 DE-16-250 04 s pos_38 2013 02 DE-16-250 05 p (DE-627)1571744517 Müller-Tidow, Carsten 2013 02 DE-16-250 05 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 02 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 02 DE-16-250 05 s pos_41 2013 02 DE-16-250 06 p (DE-627)1504263316 Dietrich, Sascha 2013 02 DE-16-250 06 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 02 DE-16-250 06 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 02 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 02 DE-16-250 06 s pos_48 |
| allfieldsGer |
10.1038/s41467-022-33385-8 doi (DE-627)1832441687 (DE-599)KXP1832441687 (OCoLC)1389536026 DE-627 ger DE-627 rda eng Herbst, Sophie 1990- verfasserin (DE-588)115041216X (DE-627)1010727222 (DE-576)497048604 aut Proteogenomics refines the molecular classification of chronic lymphocytic leukemia Sophie A. Herbst, Mattias Vesterlund, Alexander J. Helmboldt, Rozbeh Jafari, Ioannis Siavelis, Matthias Stahl, Eva C. Schitter, Nora Liebers, Berit J. Brinkmann, Felix Czernilofsky, Tobias Roider, Peter-Martin Bruch, Murat Iskar, Adam Kittai, Ying Huang, Junyan Lu, Sarah Richter, Georgios Mermelekas, Husen Muhammad Umer, Mareike Knoll, Carolin Kolb, Angela Lenze, Xiaofang Cao, Cecilia Österholm, Linus Wahnschaffe, Carmen Herling, Sebastian Scheinost, Matthias Ganzinger, Larry Mansouri, Katharina Kriegsmann, Mark Kriegsmann, Simon Anders, Marc Zapatka, Giovanni Del Poeta, Antonella Zucchetto, Riccardo Bomben, Valter Gattei, Peter Dreger, Jennifer Woyach, Marco Herling, Carsten Müller-Tidow, Richard Rosenquist, Stephan Stilgenbauer, Thorsten Zenz, Wolfgang Huber, Eugen Tausch, Janne Lehtiö, Sascha Dietrich 20 October 2022 18 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 25.01.2023 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. Chronic lymphocytic leukaemia Computational models Proteomic analysis Vesterlund, Mattias verfasserin aut Helmboldt, Alexander verfasserin aut Jafari, Rozbeh verfasserin aut Siavelis, Ioannis verfasserin aut Stahl, Matthias verfasserin aut Schitter, Eva C. 1994- verfasserin (DE-588)1323489495 (DE-627)1883461227 aut Liebers, Nora 1989- verfasserin (DE-588)1123162875 (DE-627)879999578 (DE-576)481643850 aut Brinkmann, Berit J. 1993- verfasserin (DE-588)124968384X (DE-627)1786214849 aut Czernilofsky, Felix verfasserin (DE-588)1246918250 (DE-627)1780154399 aut Roider, Tobias 1988- verfasserin (DE-588)112919017X (DE-627)883826232 (DE-576)486252264 aut Bruch, Peter-Martin 1993- verfasserin (DE-588)1203140363 (DE-627)168794198X aut Iskar, Murat verfasserin aut Kittai, Adam verfasserin aut Huang, Ying verfasserin aut Lu, Junyan verfasserin (DE-588)124416478X (DE-627)1775109585 aut Richter, Sarah verfasserin (DE-588)1279135522 (DE-627)1832443124 aut Mermelekas, Georgios verfasserin aut Umer, Husen Muhammad verfasserin aut Knoll, Mareike verfasserin (DE-588)1279136073 (DE-627)183244323X aut Kolb, Carolin verfasserin (DE-588)1325175609 (DE-627)1884945163 aut Lenze, Angela verfasserin (DE-588)1279136545 (DE-627)1832443442 aut Cao, Xiaofang verfasserin aut Österholm, Cecilia verfasserin aut Wahnschaffe, Linus verfasserin aut Herling, Carmen verfasserin aut Scheinost, Sebastian verfasserin (DE-588)1203319711 (DE-627)168814305X aut Ganzinger, Matthias 1974- verfasserin (DE-588)102301890X (DE-627)717346471 (DE-576)366268082 aut Mansouri, Larry verfasserin aut Kriegsmann, Katharina 1986- verfasserin (DE-588)1049422449 (DE-627)781924006 (DE-576)40339774X aut Kriegsmann, Mark 1987- verfasserin (DE-588)103740324X (DE-627)755668782 (DE-576)39141870X aut Anders, Simon verfasserin (DE-588)1184492964 (DE-627)1663597936 aut Zapatka, Marc 1974- verfasserin (DE-588)128629975 (DE-627)376935782 (DE-576)297249320 aut Del Poeta, Giovanni verfasserin aut Zucchetto, Antonella verfasserin aut Bomben, Riccardo verfasserin aut Gattei, Valter verfasserin aut Dreger, Peter verfasserin (DE-588)1028891881 (DE-627)732699894 (DE-576)376320966 aut Woyach, Jennifer verfasserin aut Herling, Marco verfasserin aut Müller-Tidow, Carsten verfasserin (DE-588)1015101798 (DE-627)705330230 (DE-576)351197893 aut Rosenquist, Richard verfasserin aut Stilgenbauer, Stephan verfasserin aut Zenz, Thorsten 1970- verfasserin (DE-588)114963738 (DE-627)577184202 (DE-576)180278266 aut Huber, Wolfgang verfasserin (DE-588)1115277685 (DE-627)870097997 (DE-576)477724442 aut Tausch, Eugen verfasserin aut Lehtiö, Janne verfasserin aut Dietrich, Sascha 1979- verfasserin (DE-588)136406300 (DE-627)694354635 (DE-576)301003408 aut Enthalten in Nature Communications [London] : Springer Nature, 2010 13(2022) vom: Okt., Artikel-ID 6226, Seite 1-18 Online-Ressource (DE-627)626457688 (DE-600)2553671-0 (DE-576)331555905 2041-1723 nnns volume:13 year:2022 month:10 elocationid:6226 pages:1-18 extent:18 https://doi.org/10.1038/s41467-022-33385-8 Verlag Resolving-System kostenfrei Volltext https://www.nature.com/articles/s41467-022-33385-8 Verlag kostenfrei Volltext GBV_USEFLAG_U GBV_ILN_2011 ISIL_DE-16 SYSFLAG_1 GBV_KXP SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2110 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 GBV_ILN_2013 GBV_ILN_2403 GBV_ILN_2013 ISIL_DE-16-250 GBV_ILN_2403 ISIL_DE-LFER AR 13 2022 10 6226 1-18 18 2011 01 DE-16 4455970592 00 --%%-- --%%-- --%%-- --%%-- l01 12-01-24 2013 01 DE-16-250 4251589254 00 --%%-- --%%-- --%%-- --%%-- l01 25-01-23 2013 02 DE-16-250 425159598X 00 --%%-- --%%-- --%%-- --%%-- l02 25-01-23 2403 01 DE-LFER 4476333125 00 --%%-- --%%-- n --%%-- l01 05-02-24 2403 01 DE-LFER https://doi.org/10.1038/s41467-022-33385-8 2403 01 DE-LFER https://www.nature.com/articles/s41467-022-33385-8 2013 01 DE-16-250 00 s hd2022 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_48 2013 01 DE-16-250 03 s s_18 2013 01 DE-16-250 04 p (DE-627)1567052428 Herbst, Sophie 2013 01 DE-16-250 04 k (DE-627)1416822720 Extern 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_1 2013 01 DE-16-250 05 p (DE-627)1551644037 Liebers, Nora 2013 01 DE-16-250 05 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_8 2013 01 DE-16-250 06 p (DE-627)1786214857 Brinkmann, Berit J. 2013 01 DE-16-250 06 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 06 s pos_9 2013 01 DE-16-250 07 p (DE-627)1780154534 Czernilofsky, Felix 2013 01 DE-16-250 07 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 07 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 07 s pos_10 2013 01 DE-16-250 08 p (DE-627)1571891331 Roider, Tobias 2013 01 DE-16-250 08 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 08 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 08 s pos_11 2013 01 DE-16-250 09 p (DE-627)1687959978 Bruch, Peter-Martin 2013 01 DE-16-250 09 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 09 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 09 s pos_12 2013 01 DE-16-250 10 p (DE-627)1775109623 Lu, Junyan 2013 01 DE-16-250 10 k (DE-627)1495544966 Zentrum für Infektiologie 2013 01 DE-16-250 10 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 10 s pos_16 2013 01 DE-16-250 11 p (DE-627)1832443132 Richter, Sarah 2013 01 DE-16-250 11 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 11 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 11 s pos_17 2013 01 DE-16-250 12 p (DE-627)1832443256 Knoll, Mareike 2013 01 DE-16-250 12 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 12 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 12 s pos_20 2013 01 DE-16-250 13 p (DE-627)1884945511 Kolb, Carolin 2013 01 DE-16-250 13 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 13 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 13 s pos_21 2013 01 DE-16-250 14 p (DE-627)1832443469 Lenze, Angela 2013 01 DE-16-250 14 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 14 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 14 s pos_22 2013 01 DE-16-250 15 p (DE-627)1492819603 Ganzinger, Matthias 2013 01 DE-16-250 15 k (DE-627)1888973080 Institut für Medizinische Informatik 2013 01 DE-16-250 15 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 15 s pos_28 2013 01 DE-16-250 16 p (DE-627)1576519953 Kriegsmann, Katharina 2013 01 DE-16-250 16 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 16 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 16 s pos_30 2013 01 DE-16-250 17 p (DE-627)1480997641 Kriegsmann, Mark 2013 01 DE-16-250 17 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 17 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 17 s pos_31 2013 01 DE-16-250 18 p (DE-627)1663598371 Anders, Simon 2013 01 DE-16-250 18 k (DE-627)1416734031 BIOQUANT 2013 01 DE-16-250 18 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 18 s pos_32 2013 01 DE-16-250 19 p (DE-627)1550450158 Zapatka, Marc 2013 01 DE-16-250 19 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 19 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 19 s pos_33 2013 02 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| allfieldsSound |
10.1038/s41467-022-33385-8 doi (DE-627)1832441687 (DE-599)KXP1832441687 (OCoLC)1389536026 DE-627 ger DE-627 rda eng Herbst, Sophie 1990- verfasserin (DE-588)115041216X (DE-627)1010727222 (DE-576)497048604 aut Proteogenomics refines the molecular classification of chronic lymphocytic leukemia Sophie A. Herbst, Mattias Vesterlund, Alexander J. Helmboldt, Rozbeh Jafari, Ioannis Siavelis, Matthias Stahl, Eva C. Schitter, Nora Liebers, Berit J. Brinkmann, Felix Czernilofsky, Tobias Roider, Peter-Martin Bruch, Murat Iskar, Adam Kittai, Ying Huang, Junyan Lu, Sarah Richter, Georgios Mermelekas, Husen Muhammad Umer, Mareike Knoll, Carolin Kolb, Angela Lenze, Xiaofang Cao, Cecilia Österholm, Linus Wahnschaffe, Carmen Herling, Sebastian Scheinost, Matthias Ganzinger, Larry Mansouri, Katharina Kriegsmann, Mark Kriegsmann, Simon Anders, Marc Zapatka, Giovanni Del Poeta, Antonella Zucchetto, Riccardo Bomben, Valter Gattei, Peter Dreger, Jennifer Woyach, Marco Herling, Carsten Müller-Tidow, Richard Rosenquist, Stephan Stilgenbauer, Thorsten Zenz, Wolfgang Huber, Eugen Tausch, Janne Lehtiö, Sascha Dietrich 20 October 2022 18 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 25.01.2023 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. Chronic lymphocytic leukaemia Computational models Proteomic analysis Vesterlund, Mattias verfasserin aut Helmboldt, Alexander verfasserin aut Jafari, Rozbeh verfasserin aut Siavelis, Ioannis verfasserin aut Stahl, Matthias verfasserin aut Schitter, Eva C. 1994- verfasserin (DE-588)1323489495 (DE-627)1883461227 aut Liebers, Nora 1989- verfasserin (DE-588)1123162875 (DE-627)879999578 (DE-576)481643850 aut Brinkmann, Berit J. 1993- verfasserin (DE-588)124968384X (DE-627)1786214849 aut Czernilofsky, Felix verfasserin (DE-588)1246918250 (DE-627)1780154399 aut Roider, Tobias 1988- verfasserin (DE-588)112919017X (DE-627)883826232 (DE-576)486252264 aut Bruch, Peter-Martin 1993- verfasserin (DE-588)1203140363 (DE-627)168794198X aut Iskar, Murat verfasserin aut Kittai, Adam verfasserin aut Huang, Ying verfasserin aut Lu, Junyan verfasserin (DE-588)124416478X (DE-627)1775109585 aut Richter, Sarah verfasserin (DE-588)1279135522 (DE-627)1832443124 aut Mermelekas, Georgios verfasserin aut Umer, Husen Muhammad verfasserin aut Knoll, Mareike verfasserin (DE-588)1279136073 (DE-627)183244323X aut Kolb, Carolin verfasserin (DE-588)1325175609 (DE-627)1884945163 aut Lenze, Angela verfasserin (DE-588)1279136545 (DE-627)1832443442 aut Cao, Xiaofang verfasserin aut Österholm, Cecilia verfasserin aut Wahnschaffe, Linus verfasserin aut Herling, Carmen verfasserin aut Scheinost, Sebastian verfasserin (DE-588)1203319711 (DE-627)168814305X aut Ganzinger, Matthias 1974- verfasserin (DE-588)102301890X (DE-627)717346471 (DE-576)366268082 aut Mansouri, Larry verfasserin aut Kriegsmann, Katharina 1986- verfasserin (DE-588)1049422449 (DE-627)781924006 (DE-576)40339774X aut Kriegsmann, Mark 1987- verfasserin (DE-588)103740324X (DE-627)755668782 (DE-576)39141870X aut Anders, Simon verfasserin (DE-588)1184492964 (DE-627)1663597936 aut Zapatka, Marc 1974- verfasserin (DE-588)128629975 (DE-627)376935782 (DE-576)297249320 aut Del Poeta, Giovanni verfasserin aut Zucchetto, Antonella verfasserin aut Bomben, Riccardo verfasserin aut Gattei, Valter verfasserin aut Dreger, Peter verfasserin (DE-588)1028891881 (DE-627)732699894 (DE-576)376320966 aut Woyach, Jennifer verfasserin aut Herling, Marco verfasserin aut Müller-Tidow, Carsten verfasserin (DE-588)1015101798 (DE-627)705330230 (DE-576)351197893 aut Rosenquist, Richard verfasserin aut Stilgenbauer, Stephan verfasserin aut Zenz, Thorsten 1970- verfasserin (DE-588)114963738 (DE-627)577184202 (DE-576)180278266 aut Huber, Wolfgang verfasserin (DE-588)1115277685 (DE-627)870097997 (DE-576)477724442 aut Tausch, Eugen verfasserin aut Lehtiö, Janne verfasserin aut Dietrich, Sascha 1979- verfasserin (DE-588)136406300 (DE-627)694354635 (DE-576)301003408 aut Enthalten in Nature Communications [London] : Springer Nature, 2010 13(2022) vom: Okt., Artikel-ID 6226, Seite 1-18 Online-Ressource (DE-627)626457688 (DE-600)2553671-0 (DE-576)331555905 2041-1723 nnns volume:13 year:2022 month:10 elocationid:6226 pages:1-18 extent:18 https://doi.org/10.1038/s41467-022-33385-8 Verlag Resolving-System kostenfrei Volltext https://www.nature.com/articles/s41467-022-33385-8 Verlag kostenfrei Volltext GBV_USEFLAG_U GBV_ILN_2011 ISIL_DE-16 SYSFLAG_1 GBV_KXP SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2110 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 GBV_ILN_2013 GBV_ILN_2403 GBV_ILN_2013 ISIL_DE-16-250 GBV_ILN_2403 ISIL_DE-LFER AR 13 2022 10 6226 1-18 18 2011 01 DE-16 4455970592 00 --%%-- --%%-- --%%-- --%%-- l01 12-01-24 2013 01 DE-16-250 4251589254 00 --%%-- --%%-- --%%-- --%%-- l01 25-01-23 2013 02 DE-16-250 425159598X 00 --%%-- --%%-- --%%-- --%%-- l02 25-01-23 2403 01 DE-LFER 4476333125 00 --%%-- --%%-- n --%%-- l01 05-02-24 2403 01 DE-LFER https://doi.org/10.1038/s41467-022-33385-8 2403 01 DE-LFER https://www.nature.com/articles/s41467-022-33385-8 2013 01 DE-16-250 00 s hd2022 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_48 2013 01 DE-16-250 03 s s_18 2013 01 DE-16-250 04 p (DE-627)1567052428 Herbst, Sophie 2013 01 DE-16-250 04 k (DE-627)1416822720 Extern 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_1 2013 01 DE-16-250 05 p (DE-627)1551644037 Liebers, Nora 2013 01 DE-16-250 05 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_8 2013 01 DE-16-250 06 p (DE-627)1786214857 Brinkmann, Berit J. 2013 01 DE-16-250 06 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 06 s pos_9 2013 01 DE-16-250 07 p (DE-627)1780154534 Czernilofsky, Felix 2013 01 DE-16-250 07 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 07 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 07 s pos_10 2013 01 DE-16-250 08 p (DE-627)1571891331 Roider, Tobias 2013 01 DE-16-250 08 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 08 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 08 s pos_11 2013 01 DE-16-250 09 p (DE-627)1687959978 Bruch, Peter-Martin 2013 01 DE-16-250 09 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 09 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 09 s pos_12 2013 01 DE-16-250 10 p (DE-627)1775109623 Lu, Junyan 2013 01 DE-16-250 10 k (DE-627)1495544966 Zentrum für Infektiologie 2013 01 DE-16-250 10 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 10 s pos_16 2013 01 DE-16-250 11 p (DE-627)1832443132 Richter, Sarah 2013 01 DE-16-250 11 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 11 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 11 s pos_17 2013 01 DE-16-250 12 p (DE-627)1832443256 Knoll, Mareike 2013 01 DE-16-250 12 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 12 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 12 s pos_20 2013 01 DE-16-250 13 p (DE-627)1884945511 Kolb, Carolin 2013 01 DE-16-250 13 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 13 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 13 s pos_21 2013 01 DE-16-250 14 p (DE-627)1832443469 Lenze, Angela 2013 01 DE-16-250 14 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 14 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 14 s pos_22 2013 01 DE-16-250 15 p (DE-627)1492819603 Ganzinger, Matthias 2013 01 DE-16-250 15 k 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English |
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Enthalten in Nature Communications 13(2022) vom: Okt., Artikel-ID 6226, Seite 1-18 volume:13 year:2022 month:10 elocationid:6226 pages:1-18 extent:18 |
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Enthalten in Nature Communications 13(2022) vom: Okt., Artikel-ID 6226, Seite 1-18 volume:13 year:2022 month:10 elocationid:6226 pages:1-18 extent:18 |
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Herbst, Sophie @@aut@@ Vesterlund, Mattias @@aut@@ Helmboldt, Alexander @@aut@@ Jafari, Rozbeh @@aut@@ Siavelis, Ioannis @@aut@@ Stahl, Matthias @@aut@@ Schitter, Eva C. @@aut@@ Liebers, Nora @@aut@@ Brinkmann, Berit J. @@aut@@ Czernilofsky, Felix @@aut@@ Roider, Tobias @@aut@@ Bruch, Peter-Martin @@aut@@ Iskar, Murat @@aut@@ Kittai, Adam @@aut@@ Huang, Ying @@aut@@ Lu, Junyan @@aut@@ Richter, Sarah @@aut@@ Mermelekas, Georgios @@aut@@ Umer, Husen Muhammad @@aut@@ Knoll, Mareike @@aut@@ Kolb, Carolin @@aut@@ Lenze, Angela @@aut@@ Cao, Xiaofang @@aut@@ Österholm, Cecilia @@aut@@ Wahnschaffe, Linus @@aut@@ Herling, Carmen @@aut@@ Scheinost, Sebastian @@aut@@ Ganzinger, Matthias @@aut@@ Mansouri, Larry @@aut@@ Kriegsmann, Katharina @@aut@@ Kriegsmann, Mark @@aut@@ Anders, Simon @@aut@@ Zapatka, Marc @@aut@@ Del Poeta, Giovanni @@aut@@ Zucchetto, Antonella @@aut@@ Bomben, Riccardo @@aut@@ Gattei, Valter @@aut@@ Dreger, Peter @@aut@@ Woyach, Jennifer @@aut@@ Herling, Marco @@aut@@ Müller-Tidow, Carsten @@aut@@ Rosenquist, Richard @@aut@@ Stilgenbauer, Stephan @@aut@@ Zenz, Thorsten @@aut@@ Huber, Wolfgang @@aut@@ Tausch, Eugen @@aut@@ Lehtiö, Janne @@aut@@ Dietrich, Sascha @@aut@@ |
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Herbst, Sophie 1990- misc Chronic lymphocytic leukaemia misc Computational models misc Proteomic analysis 2013 hd2022 2013 wissenschaftlicher Artikel (Zeitschrift) 2013 per_48 2013 s_18 2013 Herbst, Sophie 2013 Extern 2013 Verfasser 2013 pos_1 2013 Liebers, Nora 2013 Zentrum für Innere Medizin (Krehl Klinik) 2013 pos_8 2013 Brinkmann, Berit J. 2013 pos_9 2013 Czernilofsky, Felix 2013 pos_10 2013 Roider, Tobias 2013 pos_11 2013 Bruch, Peter-Martin 2013 pos_12 2013 Lu, Junyan 2013 Zentrum für Infektiologie 2013 pos_16 2013 Richter, Sarah 2013 pos_17 2013 Knoll, Mareike 2013 pos_20 2013 Kolb, Carolin 2013 pos_21 2013 Lenze, Angela 2013 pos_22 2013 Ganzinger, Matthias 2013 Institut für Medizinische Informatik 2013 pos_28 2013 Kriegsmann, Katharina 2013 pos_30 2013 Kriegsmann, Mark 2013 Medizinische Fakultät Heidelberg 2013 pos_31 2013 Anders, Simon 2013 BIOQUANT 2013 pos_32 2013 Zapatka, Marc 2013 pos_33 2013 Dreger, Peter 2013 pos_38 2013 Müller-Tidow, Carsten 2013 pos_41 2013 Dietrich, Sascha 2013 pos_48 Proteogenomics refines the molecular classification of chronic lymphocytic leukemia |
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2013 01 DE-16-250 00 s hd2022 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_48 2013 01 DE-16-250 03 s s_18 2013 01 DE-16-250 04 p (DE-627)1567052428 Herbst, Sophie 2013 01 DE-16-250 04 k (DE-627)1416822720 Extern 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_1 2013 01 DE-16-250 05 p (DE-627)1551644037 Liebers, Nora 2013 01 DE-16-250 05 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_8 2013 01 DE-16-250 06 p (DE-627)1786214857 Brinkmann, Berit J. 2013 01 DE-16-250 06 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 06 s pos_9 2013 01 DE-16-250 07 p (DE-627)1780154534 Czernilofsky, Felix 2013 01 DE-16-250 07 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 07 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 07 s pos_10 2013 01 DE-16-250 08 p (DE-627)1571891331 Roider, Tobias 2013 01 DE-16-250 08 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 08 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 08 s pos_11 2013 01 DE-16-250 09 p (DE-627)1687959978 Bruch, Peter-Martin 2013 01 DE-16-250 09 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 09 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 09 s pos_12 2013 01 DE-16-250 10 p (DE-627)1775109623 Lu, Junyan 2013 01 DE-16-250 10 k (DE-627)1495544966 Zentrum für Infektiologie 2013 01 DE-16-250 10 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 10 s pos_16 2013 01 DE-16-250 11 p (DE-627)1832443132 Richter, Sarah 2013 01 DE-16-250 11 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 11 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 11 s pos_17 2013 01 DE-16-250 12 p (DE-627)1832443256 Knoll, Mareike 2013 01 DE-16-250 12 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 12 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 12 s pos_20 2013 01 DE-16-250 13 p (DE-627)1884945511 Kolb, Carolin 2013 01 DE-16-250 13 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 13 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 13 s pos_21 2013 01 DE-16-250 14 p (DE-627)1832443469 Lenze, Angela 2013 01 DE-16-250 14 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 14 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 14 s pos_22 2013 01 DE-16-250 15 p (DE-627)1492819603 Ganzinger, Matthias 2013 01 DE-16-250 15 k (DE-627)1888973080 Institut für Medizinische Informatik 2013 01 DE-16-250 15 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 15 s pos_28 2013 01 DE-16-250 16 p (DE-627)1576519953 Kriegsmann, Katharina 2013 01 DE-16-250 16 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 01 DE-16-250 16 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 16 s pos_30 2013 01 DE-16-250 17 p (DE-627)1480997641 Kriegsmann, Mark 2013 01 DE-16-250 17 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 17 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 17 s pos_31 2013 01 DE-16-250 18 p (DE-627)1663598371 Anders, Simon 2013 01 DE-16-250 18 k (DE-627)1416734031 BIOQUANT 2013 01 DE-16-250 18 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 18 s pos_32 2013 01 DE-16-250 19 p (DE-627)1550450158 Zapatka, Marc 2013 01 DE-16-250 19 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 19 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 19 s pos_33 2013 02 DE-16-250 00 s hd2022 2013 02 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 02 DE-16-250 02 s per_48 2013 02 DE-16-250 03 s s_18 2013 02 DE-16-250 04 p (DE-627)1447864395 Dreger, Peter 2013 02 DE-16-250 04 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 02 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 02 DE-16-250 04 s pos_38 2013 02 DE-16-250 05 p (DE-627)1571744517 Müller-Tidow, Carsten 2013 02 DE-16-250 05 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 02 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 02 DE-16-250 05 s pos_41 2013 02 DE-16-250 06 p (DE-627)1504263316 Dietrich, Sascha 2013 02 DE-16-250 06 k (DE-627)169133667X Zentrum für Innere Medizin (Krehl Klinik) 2013 02 DE-16-250 06 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 02 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 02 DE-16-250 06 s pos_48 Proteogenomics refines the molecular classification of chronic lymphocytic leukemia Sophie A. Herbst, Mattias Vesterlund, Alexander J. Helmboldt, Rozbeh Jafari, Ioannis Siavelis, Matthias Stahl, Eva C. Schitter, Nora Liebers, Berit J. Brinkmann, Felix Czernilofsky, Tobias Roider, Peter-Martin Bruch, Murat Iskar, Adam Kittai, Ying Huang, Junyan Lu, Sarah Richter, Georgios Mermelekas, Husen Muhammad Umer, Mareike Knoll, Carolin Kolb, Angela Lenze, Xiaofang Cao, Cecilia Österholm, Linus Wahnschaffe, Carmen Herling, Sebastian Scheinost, Matthias Ganzinger, Larry Mansouri, Katharina Kriegsmann, Mark Kriegsmann, Simon Anders, Marc Zapatka, Giovanni Del Poeta, Antonella Zucchetto, Riccardo Bomben, Valter Gattei, Peter Dreger, Jennifer Woyach, Marco Herling, Carsten Müller-Tidow, Richard Rosenquist, Stephan Stilgenbauer, Thorsten Zenz, Wolfgang Huber, Eugen Tausch, Janne Lehtiö, Sascha Dietrich Chronic lymphocytic leukaemia Computational models Proteomic analysis |
| topic |
misc Chronic lymphocytic leukaemia misc Computational models misc Proteomic analysis 2013 hd2022 2013 wissenschaftlicher Artikel (Zeitschrift) 2013 per_48 2013 s_18 2013 Herbst, Sophie 2013 Extern 2013 Verfasser 2013 pos_1 2013 Liebers, Nora 2013 Zentrum für Innere Medizin (Krehl Klinik) 2013 pos_8 2013 Brinkmann, Berit J. 2013 pos_9 2013 Czernilofsky, Felix 2013 pos_10 2013 Roider, Tobias 2013 pos_11 2013 Bruch, Peter-Martin 2013 pos_12 2013 Lu, Junyan 2013 Zentrum für Infektiologie 2013 pos_16 2013 Richter, Sarah 2013 pos_17 2013 Knoll, Mareike 2013 pos_20 2013 Kolb, Carolin 2013 pos_21 2013 Lenze, Angela 2013 pos_22 2013 Ganzinger, Matthias 2013 Institut für Medizinische Informatik 2013 pos_28 2013 Kriegsmann, Katharina 2013 pos_30 2013 Kriegsmann, Mark 2013 Medizinische Fakultät Heidelberg 2013 pos_31 2013 Anders, Simon 2013 BIOQUANT 2013 pos_32 2013 Zapatka, Marc 2013 pos_33 2013 Dreger, Peter 2013 pos_38 2013 Müller-Tidow, Carsten 2013 pos_41 2013 Dietrich, Sascha 2013 pos_48 |
| topic_unstemmed |
misc Chronic lymphocytic leukaemia misc Computational models misc Proteomic analysis 2013 hd2022 2013 wissenschaftlicher Artikel (Zeitschrift) 2013 per_48 2013 s_18 2013 Herbst, Sophie 2013 Extern 2013 Verfasser 2013 pos_1 2013 Liebers, Nora 2013 Zentrum für Innere Medizin (Krehl Klinik) 2013 pos_8 2013 Brinkmann, Berit J. 2013 pos_9 2013 Czernilofsky, Felix 2013 pos_10 2013 Roider, Tobias 2013 pos_11 2013 Bruch, Peter-Martin 2013 pos_12 2013 Lu, Junyan 2013 Zentrum für Infektiologie 2013 pos_16 2013 Richter, Sarah 2013 pos_17 2013 Knoll, Mareike 2013 pos_20 2013 Kolb, Carolin 2013 pos_21 2013 Lenze, Angela 2013 pos_22 2013 Ganzinger, Matthias 2013 Institut für Medizinische Informatik 2013 pos_28 2013 Kriegsmann, Katharina 2013 pos_30 2013 Kriegsmann, Mark 2013 Medizinische Fakultät Heidelberg 2013 pos_31 2013 Anders, Simon 2013 BIOQUANT 2013 pos_32 2013 Zapatka, Marc 2013 pos_33 2013 Dreger, Peter 2013 pos_38 2013 Müller-Tidow, Carsten 2013 pos_41 2013 Dietrich, Sascha 2013 pos_48 |
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misc Chronic lymphocytic leukaemia misc Computational models misc Proteomic analysis 2013 hd2022 2013 wissenschaftlicher Artikel (Zeitschrift) 2013 per_48 2013 s_18 2013 Herbst, Sophie 2013 Extern 2013 Verfasser 2013 pos_1 2013 Liebers, Nora 2013 Zentrum für Innere Medizin (Krehl Klinik) 2013 pos_8 2013 Brinkmann, Berit J. 2013 pos_9 2013 Czernilofsky, Felix 2013 pos_10 2013 Roider, Tobias 2013 pos_11 2013 Bruch, Peter-Martin 2013 pos_12 2013 Lu, Junyan 2013 Zentrum für Infektiologie 2013 pos_16 2013 Richter, Sarah 2013 pos_17 2013 Knoll, Mareike 2013 pos_20 2013 Kolb, Carolin 2013 pos_21 2013 Lenze, Angela 2013 pos_22 2013 Ganzinger, Matthias 2013 Institut für Medizinische Informatik 2013 pos_28 2013 Kriegsmann, Katharina 2013 pos_30 2013 Kriegsmann, Mark 2013 Medizinische Fakultät Heidelberg 2013 pos_31 2013 Anders, Simon 2013 BIOQUANT 2013 pos_32 2013 Zapatka, Marc 2013 pos_33 2013 Dreger, Peter 2013 pos_38 2013 Müller-Tidow, Carsten 2013 pos_41 2013 Dietrich, Sascha 2013 pos_48 |
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Proteogenomics refines the molecular classification of chronic lymphocytic leukemia Sophie A. Herbst, Mattias Vesterlund, Alexander J. Helmboldt, Rozbeh Jafari, Ioannis Siavelis, Matthias Stahl, Eva C. Schitter, Nora Liebers, Berit J. Brinkmann, Felix Czernilofsky, Tobias Roider, Peter-Martin Bruch, Murat Iskar, Adam Kittai, Ying Huang, Junyan Lu, Sarah Richter, Georgios Mermelekas, Husen Muhammad Umer, Mareike Knoll, Carolin Kolb, Angela Lenze, Xiaofang Cao, Cecilia Österholm, Linus Wahnschaffe, Carmen Herling, Sebastian Scheinost, Matthias Ganzinger, Larry Mansouri, Katharina Kriegsmann, Mark Kriegsmann, Simon Anders, Marc Zapatka, Giovanni Del Poeta, Antonella Zucchetto, Riccardo Bomben, Valter Gattei, Peter Dreger, Jennifer Woyach, Marco Herling, Carsten Müller-Tidow, Richard Rosenquist, Stephan Stilgenbauer, Thorsten Zenz, Wolfgang Huber, Eugen Tausch, Janne Lehtiö, Sascha Dietrich |
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proteogenomics refines the molecular classification of chronic lymphocytic leukemia |
| title_auth |
Proteogenomics refines the molecular classification of chronic lymphocytic leukemia |
| 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. Gesehen am 25.01.2023 |
| abstractGer |
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. Gesehen am 25.01.2023 |
| abstract_unstemmed |
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. Gesehen am 25.01.2023 |
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| title_short |
Proteogenomics refines the molecular classification of chronic lymphocytic leukemia |
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https://doi.org/10.1038/s41467-022-33385-8 https://www.nature.com/articles/s41467-022-33385-8 |
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Vesterlund, Mattias Helmboldt, Alexander Jafari, Rozbeh Siavelis, Ioannis Stahl, Matthias Schitter, Eva C. 1994- Liebers, Nora 1989- Brinkmann, Berit J. 1993- Czernilofsky, Felix Roider, Tobias 1988- Bruch, Peter-Martin 1993- Iskar, Murat Kittai, Adam Huang, Ying Lu, Junyan Richter, Sarah Mermelekas, Georgios Umer, Husen Muhammad Knoll, Mareike Kolb, Carolin Lenze, Angela Cao, Xiaofang Österholm, Cecilia Wahnschaffe, Linus Herling, Carmen Scheinost, Sebastian Ganzinger, Matthias 1974- Mansouri, Larry Kriegsmann, Katharina 1986- Kriegsmann, Mark 1987- Anders, Simon Zapatka, Marc 1974- Del Poeta, Giovanni Zucchetto, Antonella Bomben, Riccardo Gattei, Valter Dreger, Peter Woyach, Jennifer Herling, Marco Müller-Tidow, Carsten Rosenquist, Richard Stilgenbauer, Stephan Zenz, Thorsten 1970- Huber, Wolfgang Tausch, Eugen Lehtiö, Janne Dietrich, Sascha 1979- |
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Herbst, Sophie A. Rabe, Sophie Herbst, Sophie Alessa Herbst, Sophie Schitter, Eva Christine Schitter, Eva C. Liebers, Nora Brinkmann, Berit Johanna Brinkmann, Berit Brinkmann, Berit J. Czernilofsky, Felix Roider, Tobias Bruch, Peter-Martin Lu, Junyan Richter, Sarah Knoll, Mareike Kolb, Carolin Lenze, Angela Scheinost, Sebastian Ganzinger, M. Ganzinger, Matthias Lisenko, Katharina Kriegsmann, K. Kriegsmann, Katharina Kriegsmann, M. Kriegsmann, Mark Bert Kriegsmann, Mark Anders, S. Anders, Simon Zapatka, Marc Dreger, P. Dreger, Peter Mueller-Tidow, Carsten Tidow, Carsten Müller- Müller-Tidow, Carsten Zenz, Thorsten Huber, Wolfgang Dietrich, Sasha Dietrich, Sascha |
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Herbst, Sophie A. Rabe, Sophie Herbst, Sophie Alessa Herbst, Sophie Schitter, Eva Christine Schitter, Eva C. Liebers, Nora Brinkmann, Berit Johanna Brinkmann, Berit Brinkmann, Berit J. Czernilofsky, Felix Roider, Tobias Bruch, Peter-Martin Lu, Junyan Richter, Sarah Knoll, Mareike Kolb, Carolin Lenze, Angela Scheinost, Sebastian Ganzinger, M. Ganzinger, Matthias Lisenko, Katharina Kriegsmann, K. Kriegsmann, Katharina Kriegsmann, M. Kriegsmann, Mark Bert Kriegsmann, Mark Anders, S. Anders, Simon Zapatka, Marc Dreger, P. Dreger, Peter Mueller-Tidow, Carsten Tidow, Carsten Müller- Müller-Tidow, Carsten Zenz, Thorsten Huber, Wolfgang Dietrich, Sasha Dietrich, Sascha |
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