Genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
15 06 2022
15 06 2022
Historique:
received:
06
05
2021
accepted:
13
05
2022
entrez:
15
6
2022
pubmed:
16
6
2022
medline:
18
6
2022
Statut:
epublish
Résumé
Smoldering multiple myeloma (SMM) is a precursor condition of multiple myeloma (MM) with significant heterogeneity in disease progression. Existing clinical models of progression risk do not fully capture this heterogeneity. Here we integrate 42 genetic alterations from 214 SMM patients using unsupervised binary matrix factorization (BMF) clustering and identify six distinct genetic subtypes. These subtypes are differentially associated with established MM-related RNA signatures, oncogenic and immune transcriptional profiles, and evolving clinical biomarkers. Three genetic subtypes are associated with increased risk of progression to active MM in both the primary and validation cohorts, indicating they can be used to better predict high and low-risk patients within the currently used clinical risk stratification models.
Identifiants
pubmed: 35705541
doi: 10.1038/s41467-022-30694-w
pii: 10.1038/s41467-022-30694-w
pmc: PMC9200804
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3449Subventions
Organisme : Cancer Research UK
ID : A28770
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Medical Research Council
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : R01 CA205954
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA186781
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM121176
Pays : United States
Informations de copyright
© 2022. The Author(s).
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