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Spatial genomic heterogeneity in multiple myeloma revealed by multi-region sequencing

Author

Listed:
  • L. Rasche

    (University of Arkansas for Medical Sciences)

  • S. S. Chavan

    (University of Arkansas for Medical Sciences)

  • O. W. Stephens

    (University of Arkansas for Medical Sciences)

  • P. H. Patel

    (University of Arkansas for Medical Sciences)

  • R. Tytarenko

    (University of Arkansas for Medical Sciences)

  • C. Ashby

    (University of Arkansas for Medical Sciences)

  • M. Bauer

    (University of Arkansas for Medical Sciences)

  • C. Stein

    (University of Arkansas for Medical Sciences)

  • S. Deshpande

    (University of Arkansas for Medical Sciences)

  • C. Wardell

    (University of Arkansas for Medical Sciences)

  • T. Buzder

    (University of Arkansas for Medical Sciences)

  • G. Molnar

    (University of Arkansas for Medical Sciences)

  • M. Zangari

    (University of Arkansas for Medical Sciences)

  • F. Rhee

    (University of Arkansas for Medical Sciences)

  • S. Thanendrarajan

    (University of Arkansas for Medical Sciences)

  • C. Schinke

    (University of Arkansas for Medical Sciences)

  • J. Epstein

    (University of Arkansas for Medical Sciences)

  • F. E. Davies

    (University of Arkansas for Medical Sciences)

  • B. A. Walker

    (University of Arkansas for Medical Sciences)

  • T. Meissner

    (Avera Cancer Institute)

  • B. Barlogie

    (University of Arkansas for Medical Sciences)

  • G. J. Morgan

    (University of Arkansas for Medical Sciences)

  • N. Weinhold

    (University of Arkansas for Medical Sciences)

Abstract

In multiple myeloma malignant plasma cells expand within the bone marrow. Since this site is well-perfused, a rapid dissemination of “fitter” clones may be anticipated. However, an imbalanced distribution of multiple myeloma is frequently observed in medical imaging. Here, we perform multi-region sequencing, including iliac crest and radiology-guided focal lesion specimens from 51 patients to gain insight into the spatial clonal architecture. We demonstrate spatial genomic heterogeneity in more than 75% of patients, including inactivation of CDKN2C and TP53, and mutations affecting mitogen-activated protein kinase genes. We show that the extent of spatial heterogeneity is positively associated with the size of biopsied focal lesions consistent with regional outgrowth of advanced clones. The results support a model for multiple myeloma progression with clonal sweeps in the early phase and regional evolution in advanced disease. We suggest that multi-region investigations are critical to understanding intra-patient heterogeneity and the evolutionary processes in multiple myeloma.

Suggested Citation

  • L. Rasche & S. S. Chavan & O. W. Stephens & P. H. Patel & R. Tytarenko & C. Ashby & M. Bauer & C. Stein & S. Deshpande & C. Wardell & T. Buzder & G. Molnar & M. Zangari & F. Rhee & S. Thanendrarajan &, 2017. "Spatial genomic heterogeneity in multiple myeloma revealed by multi-region sequencing," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00296-y
    DOI: 10.1038/s41467-017-00296-y
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    Cited by:

    1. Lukas John & Alexandra M. Poos & Alexander Brobeil & Carolina Schinke & Stefanie Huhn & Nina Prokoph & Raphael Lutz & Barbara Wagner & Maurizio Zangari & Stephan M. Tirier & Jan-Philipp Mallm & Sabrin, 2023. "Resolving the spatial architecture of myeloma and its microenvironment at the single-cell level," Nature Communications, Nature, vol. 14(1), pages 1-17, 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. Maximilian Merz & Almuth Maria Anni Merz & Jie Wang & Lei Wei & Qiang Hu & Nicholas Hutson & Cherie Rondeau & Kimberly Celotto & Ahmed Belal & Ronald Alberico & AnneMarie W. Block & Hemn Mohammadpour , 2022. "Deciphering spatial genomic heterogeneity at a single cell resolution in multiple myeloma," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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