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Whole-genome sequencing reveals progressive versus stable myeloma precursor conditions as two distinct entities

Author

Listed:
  • Bénedith Oben

    (Jessa Hospital
    Hasselt University)

  • Guy Froyen

    (Hasselt University
    Jessa Hospital)

  • Kylee H. Maclachlan

    (Memorial Sloan Kettering Cancer Center)

  • Daniel Leongamornlert

    (Wellcome Sanger Institute)

  • Federico Abascal

    (Wellcome Sanger Institute)

  • Binbin Zheng-Lin

    (Memorial Sloan Kettering Cancer Center)

  • Venkata Yellapantula

    (Memorial Sloan Kettering Cancer Center)

  • Andriy Derkach

    (Memorial Sloan Kettering Cancer Center)

  • Ellen Geerdens

    (Jessa Hospital)

  • Benjamin T. Diamond

    (Memorial Sloan Kettering Cancer Center)

  • Ingrid Arijs

    (Hasselt University
    VIB Center for Cancer Biology
    University of Leuven)

  • Brigitte Maes

    (Jessa Hospital)

  • Kimberly Vanhees

    (Hasselt University
    Clinical Biobank Jessa Hospital)

  • Malin Hultcrantz

    (Memorial Sloan Kettering Cancer Center)

  • Elisabet E. Manasanch

    (The University of Texas MD Anderson Cancer Center)

  • Dickran Kazandjian

    (National Institutes of Health)

  • Alexander Lesokhin

    (Memorial Sloan Kettering Cancer Center)

  • Ahmet Dogan

    (Memorial Sloan Kettering Cancer Center)

  • Yanming Zhang

    (Memorial Sloan Kettering Cancer Center)

  • Aneta Mikulasova

    (Newcastle University)

  • Brian Walker

    (Indiana University)

  • Gareth Morgan

    (New York University Langone Health)

  • Peter J. Campbell

    (Wellcome Sanger Institute)

  • Ola Landgren

    (University of Miami)

  • Jean-Luc Rummens

    (Jessa Hospital
    Hasselt University
    Clinical Biobank Jessa Hospital)

  • Niccolò Bolli

    (University of Milan
    Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico)

  • Francesco Maura

    (Memorial Sloan Kettering Cancer Center
    University of Miami)

Abstract

Multiple myeloma (MM) is consistently preceded by precursor conditions recognized clinically as monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM). We interrogate the whole genome sequence (WGS) profile of 18 MGUS and compare them with those from 14 SMMs and 80 MMs. We show that cases with a non-progressing, clinically stable myeloma precursor condition (n = 15) are characterized by later initiation in the patient’s life and by the absence of myeloma defining genomic events including: chromothripsis, templated insertions, mutations in driver genes, aneuploidy, and canonical APOBEC mutational activity. This data provides evidence that WGS can be used to recognize two biologically and clinically distinct myeloma precursor entities that are either progressive or stable.

Suggested Citation

  • Bénedith Oben & Guy Froyen & Kylee H. Maclachlan & Daniel Leongamornlert & Federico Abascal & Binbin Zheng-Lin & Venkata Yellapantula & Andriy Derkach & Ellen Geerdens & Benjamin T. Diamond & Ingrid A, 2021. "Whole-genome sequencing reveals progressive versus stable myeloma precursor conditions as two distinct entities," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22140-0
    DOI: 10.1038/s41467-021-22140-0
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    Cited by:

    1. Danielle C. Croucher & Laura M. Richards & Serges P. Tsofack & Daniel Waller & Zhihua Li & Ellen Nong Wei & Xian Fang Huang & Marta Chesi & P. Leif Bergsagel & Michael Sebag & Trevor J. Pugh & Suzanne, 2021. "Longitudinal single-cell analysis of a myeloma mouse model identifies subclonal molecular programs associated with progression," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    2. Rebecca Boiarsky & Nicholas J. Haradhvala & Jean-Baptiste Alberge & Romanos Sklavenitis-Pistofidis & Tarek H. Mouhieddine & Oksana Zavidij & Ming-Chieh Shih & Danielle Firer & Mendy Miller & Habib El-, 2022. "Single cell characterization of myeloma and its precursor conditions reveals transcriptional signatures of early tumorigenesis," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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