Proteogenomics refines the molecular classification of chronic lymphocytic leukemia.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
20 10 2022
20 10 2022
Historique:
received:
14
02
2022
accepted:
14
09
2022
entrez:
20
10
2022
pubmed:
21
10
2022
medline:
25
10
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36266272
doi: 10.1038/s41467-022-33385-8
pii: 10.1038/s41467-022-33385-8
pmc: PMC9584885
doi:
Substances chimiques
Proteome
0
Receptors, Antigen, B-Cell
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6226Subventions
Organisme : NCI NIH HHS
ID : R01 CA177292
Pays : United States
Informations de copyright
© 2022. The Author(s).
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