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The molecular make up of smoldering myeloma highlights the evolutionary pathways leading to multiple myeloma

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Listed:
  • Eileen M. Boyle

    (Myeloma Center, University of Arkansas for Medical Sciences
    INSERM 1052/CNRS 5286 Cancer Research Center of Lyon
    Perlmutter Cancer Center, NYU Langone Health)

  • Shayu Deshpande

    (Myeloma Center, University of Arkansas for Medical Sciences)

  • Ruslana Tytarenko

    (Myeloma Center, University of Arkansas for Medical Sciences)

  • Cody Ashby

    (Myeloma Center, University of Arkansas for Medical Sciences
    University of Arkansas for Medical Sciences)

  • Yan Wang

    (Myeloma Center, University of Arkansas for Medical Sciences)

  • Michael A. Bauer

    (Myeloma Center, University of Arkansas for Medical Sciences
    University of Arkansas for Medical Sciences)

  • Sarah K. Johnson

    (Myeloma Center, University of Arkansas for Medical Sciences)

  • Christopher P. Wardell

    (Myeloma Center, University of Arkansas for Medical Sciences
    University of Arkansas for Medical Sciences)

  • Sharmilan Thanendrarajan

    (Myeloma Center, University of Arkansas for Medical Sciences)

  • Maurizio Zangari

    (Myeloma Center, University of Arkansas for Medical Sciences)

  • Thierry Facon

    (Lille University Hospital)

  • Charles Dumontet

    (INSERM 1052/CNRS 5286 Cancer Research Center of Lyon)

  • Bart Barlogie

    (The Mount Sinai Hospital)

  • Arnaldo Arbini

    (Perlmutter Cancer Center, NYU Langone Health)

  • Even H. Rustad

    (Perlmutter Cancer Center, NYU Langone Health)

  • Francesco Maura

    (Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center)

  • Ola Landgren

    (Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center)

  • Fenghuang Zhan

    (Myeloma Center, University of Arkansas for Medical Sciences)

  • Frits Rhee

    (Myeloma Center, University of Arkansas for Medical Sciences)

  • Carolina Schinke

    (Myeloma Center, University of Arkansas for Medical Sciences)

  • Faith E. Davies

    (Perlmutter Cancer Center, NYU Langone Health)

  • Gareth J. Morgan

    (Perlmutter Cancer Center, NYU Langone Health)

  • Brian A. Walker

    (Indiana University)

Abstract

Smoldering myeloma (SMM) is associated with a high-risk of progression to myeloma (MM). We report the results of a study of 82 patients with both targeted sequencing that included a capture of the immunoglobulin and MYC regions. By comparing these results to newly diagnosed myeloma (MM) we show fewer NRAS and FAM46C mutations together with fewer adverse translocations, del(1p), del(14q), del(16q), and del(17p) in SMM consistent with their role as drivers of the transition to MM. KRAS mutations are associated with a shorter time to progression (HR 3.5 (1.5–8.1), p = 0.001). In an analysis of change in clonal structure over time we studied 53 samples from nine patients at multiple time points. Branching evolutionary patterns, novel mutations, biallelic hits in crucial tumour suppressor genes, and segmental copy number changes are key mechanisms underlying the transition to MM, which can precede progression and be used to guide early intervention strategies.

Suggested Citation

  • Eileen M. Boyle & Shayu Deshpande & Ruslana Tytarenko & Cody Ashby & Yan Wang & Michael A. Bauer & Sarah K. Johnson & Christopher P. Wardell & Sharmilan Thanendrarajan & Maurizio Zangari & Thierry Fac, 2021. "The molecular make up of smoldering myeloma highlights the evolutionary pathways leading to multiple myeloma," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20524-2
    DOI: 10.1038/s41467-020-20524-2
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    Cited by:

    1. Leo Rasche & Carolina Schinke & Francesco Maura & Michael A. Bauer & Cody Ashby & Shayu Deshpande & Alexandra M. Poos & Maurizio Zangari & Sharmilan Thanendrarajan & Faith E. Davies & Brian A. Walker , 2022. "The spatio-temporal evolution of multiple myeloma from baseline to relapse-refractory states," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. 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.

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