Molecular map of chronic lymphocytic leukemia and its impact on outcome.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
received:
30
04
2021
accepted:
21
06
2022
pubmed:
5
8
2022
medline:
15
11
2022
entrez:
4
8
2022
Statut:
ppublish
Résumé
Recent advances in cancer characterization have consistently revealed marked heterogeneity, impeding the completion of integrated molecular and clinical maps for each malignancy. Here, we focus on chronic lymphocytic leukemia (CLL), a B cell neoplasm with variable natural history that is conventionally categorized into two subtypes distinguished by extent of somatic mutations in the heavy-chain variable region of immunoglobulin genes (IGHV). To build the 'CLL map,' we integrated genomic, transcriptomic and epigenomic data from 1,148 patients. We identified 202 candidate genetic drivers of CLL (109 new) and refined the characterization of IGHV subtypes, which revealed distinct genomic landscapes and leukemogenic trajectories. Discovery of new gene expression subtypes further subcategorized this neoplasm and proved to be independent prognostic factors. Clinical outcomes were associated with a combination of genetic, epigenetic and gene expression features, further advancing our prognostic paradigm. Overall, this work reveals fresh insights into CLL oncogenesis and prognostication.
Identifiants
pubmed: 35927489
doi: 10.1038/s41588-022-01140-w
pii: 10.1038/s41588-022-01140-w
pmc: PMC10084830
mid: NIHMS1882834
doi:
Substances chimiques
Immunoglobulin Variable Region
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1664-1674Subventions
Organisme : NHGRI NIH HHS
ID : T32 HG002295
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL116324
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA213442
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA206978
Pays : United States
Organisme : NCI NIH HHS
ID : R50 CA251956
Pays : United States
Organisme : Cancer Research UK
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.
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