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

Author

Listed:
  • Mark Bustoros

    (Dana-Farber Cancer Center
    Weill Cornell Medicine)

  • Shankara Anand

    (Broad Institute of MIT & Harvard
    Boston University School of Medicine)

  • Romanos Sklavenitis-Pistofidis

    (Dana-Farber Cancer Center
    Broad Institute of MIT & Harvard)

  • 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
    University of Münster Medical School)

  • 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
    Massachusetts General Hospital Cancer Center)

  • Irene M. Ghobrial

    (Dana-Farber Cancer Center
    Broad Institute of MIT & Harvard)

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.

Suggested Citation

  • 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 Neu, 2022. "Genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30694-w
    DOI: 10.1038/s41467-022-30694-w
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