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Genomic patterns of progression in smoldering multiple myeloma

Author

Listed:
  • Niccolò Bolli

    (University of Milan
    Fondazione IRCCS Istituto Nazionale dei Tumori
    Wellcome Trust Sanger Institute)

  • Francesco Maura

    (University of Milan
    Wellcome Trust Sanger Institute)

  • Stephane Minvielle

    (Université de Nantes, Université d’Angers
    CHU de Nantes)

  • Dominik Gloznik

    (Wellcome Trust Sanger Institute)

  • Raphael Szalat

    (Harvard Medical School)

  • Anthony Fullam

    (Wellcome Trust Sanger Institute)

  • Inigo Martincorena

    (Wellcome Trust Sanger Institute)

  • Kevin J. Dawson

    (Wellcome Trust Sanger Institute)

  • Mehmet Kemal Samur

    (Harvard Medical School)

  • Jorge Zamora

    (Wellcome Trust Sanger Institute)

  • Patrick Tarpey

    (Wellcome Trust Sanger Institute)

  • Helen Davies

    (Wellcome Trust Sanger Institute)

  • Mariateresa Fulciniti

    (Harvard Medical School)

  • Masood A. Shammas

    (Harvard Medical School)

  • Yu Tzu Tai

    (Harvard Medical School)

  • Florence Magrangeas

    (Université de Nantes, Université d’Angers
    CHU de Nantes)

  • Philippe Moreau

    (Université de Nantes, Université d’Angers
    CHU de Nantes)

  • Paolo Corradini

    (University of Milan
    Fondazione IRCCS Istituto Nazionale dei Tumori)

  • Kenneth Anderson

    (Harvard Medical School)

  • Ludmil Alexandrov

    (University of California, San Diego)

  • David C. Wedge

    (University of Oxford)

  • Herve Avet-Loiseau

    (L’Institut Universitaire du Cancer Oncopole)

  • Peter Campbell

    (University of Milan)

  • Nikhil Munshi

    (Harvard Medical School
    Veterans Administration Boston Healthcare System)

Abstract

We analyzed whole genomes of unique paired samples from smoldering multiple myeloma (SMM) patients progressing to multiple myeloma (MM). We report that the genomic landscape, including mutational profile and structural rearrangements at the smoldering stage is very similar to MM. Paired sample analysis shows two different patterns of progression: a “static progression model”, where the subclonal architecture is retained as the disease progressed to MM suggesting that progression solely reflects the time needed to accumulate a sufficient disease burden; and a “spontaneous evolution model”, where a change in the subclonal composition is observed. We also observe that activation-induced cytidine deaminase plays a major role in shaping the mutational landscape of early subclinical phases, while progression is driven by APOBEC cytidine deaminases. These results provide a unique insight into myelomagenesis with potential implications for the definition of smoldering disease and timing of treatment initiation.

Suggested Citation

  • Niccolò Bolli & Francesco Maura & Stephane Minvielle & Dominik Gloznik & Raphael Szalat & Anthony Fullam & Inigo Martincorena & Kevin J. Dawson & Mehmet Kemal Samur & Jorge Zamora & Patrick Tarpey & H, 2018. "Genomic patterns of progression in smoldering multiple myeloma," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05058-y
    DOI: 10.1038/s41467-018-05058-y
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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. 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.
    3. 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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