Genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes

Mark Bustoros, Shankara Anand, Romanos Sklavenitis-Pistofidis, Robert Redd, Eileen M. Boyle, Benny Zhitomirsky, Andrew J. Dunford, Yu-Tzu Tai, Selina J. Chavda, Cody Boehner, Carl Jannes Neuse, Mahshid Rahmat, Ankit Dutta, Tineke Casneuf, Raluca Verona, Efstathis Kastritis, Lorenzo Trippa, Chip Stewart, Brian A. Walker, Faith E. Davies, Meletios-Athanasios Dimopoulos, P. Leif Bergsagel, Kwee Yong, Gareth J. Morgan, François Aguet, Gad Getz () and Irene M. Ghobrial ()
Additional contact information
Mark Bustoros: Dana-Farber Cancer Center
Shankara Anand: Broad Institute of MIT & Harvard
Romanos Sklavenitis-Pistofidis: Dana-Farber Cancer Center
Robert Redd: Dana-Farber Cancer Institute
Eileen M. Boyle: NYU Langone Health
Benny Zhitomirsky: Broad Institute of MIT & Harvard
Andrew J. Dunford: Broad Institute of MIT & Harvard
Yu-Tzu Tai: Dana-Farber Cancer Center
Selina J. Chavda: University College London
Cody Boehner: Dana-Farber Cancer Center
Carl Jannes Neuse: Dana-Farber Cancer Center
Mahshid Rahmat: Dana-Farber Cancer Center
Ankit Dutta: Dana-Farber Cancer Center
Tineke Casneuf: Janssen Research and Development
Raluca Verona: Janssen Research and Development
Efstathis Kastritis: National and Kapodistrian University of Athens
Lorenzo Trippa: Dana-Farber Cancer Institute
Chip Stewart: Broad Institute of MIT & Harvard
Brian A. Walker: Indiana University
Faith E. Davies: NYU Langone Health
Meletios-Athanasios Dimopoulos: National and Kapodistrian University of Athens
P. Leif Bergsagel: Mayo Clinic
Kwee Yong: University College London
Gareth J. Morgan: NYU Langone Health
François Aguet: Broad Institute of MIT & Harvard
Gad Getz: Broad Institute of MIT & Harvard
Irene M. Ghobrial: Dana-Farber Cancer Center

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: Abstract 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30694-w

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DOI: 10.1038/s41467-022-30694-w

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