IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_s41467-017-00296-y.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-017-00296-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-017-00296-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    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.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00296-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.