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Cited by 417Multiple Myeloma Research and TreatmentsCancer Genomics and DiagnosticsAcute Myeloid Leukemia Research

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

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Rasche, L., Chavan, S. S., Stephens, O. W., Patel, P. H., Tytarenko, R., Ashby, C., Bauer, M., Stein, C. +15 more·2017·Nature Communications
DOI 10.1038/s41467-017-00296-yPMC PMC5559527
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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.

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  • There is a model with three major groups of MGUS/SMM.

    “Overall, these patterns combined with observations from epidemiological studies suggest a model with three major groups of MGUS/SMM (Figure 3).84,86”

    From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [86]

    The Discussion (Fig. 5; page unavailable) proposes a two-phase model of clonal progression in multiple myeloma, with MGUS mentioned as an earlier stage. Our copy does not describe three major groups of MGUS/SMM; searches for that grouping and for epidemiological evidence found no supporting passage. (LLM, conf=0.73)

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Authors
Rasche, L., Chavan, S. S., Stephens, O. W., Patel, P. H., Tytarenko, R., Ashby, C., Bauer, M., Stein, C., Deshpande, S., Wardell, C., Buzder, T., Molnar, G., Zangari, M., van Rhee, F., Thanendrarajan, S., Schinke, C., Epstein, J., Davies, F. E., Walker, B. A., Meissner, T., Barlogie, B., Morgan, G. J., & Weinhold, N.
Affiliations
  • University of Arkansas for Medical Sciences (US)
  • Avera Health (US)
Corresponding author
Weinhold, N.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2017-08-16
Volume
8
Issue
1
Pages
268-268
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-017-00296-y
PMC
PMC5559527
OpenAlex
W2744373774
Cited by
417
References
7
Citations by year
2026: 34 · 2025: 48 · 2024: 47 · 2023: 45 · 2022: 62 · 2021: 53 · 2020: 45 · 2019: 39 · 2018: 40 · 2017: 2
FWCI
26.56
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Deutsche Forschungsgemeinschaft
  • National Cancer Institute (P01CA055819)
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
Keywords
multiple myeloma, clonal architecture, intra-tumour heterogeneity, clonal evolution, focal lesions, p53 inactivation, tumor progression, bone marrow
MeSH terms
Aged, Aged, 80 and over, Bone Marrow, Female, Fibroblast Growth Factors, Humans, Male, Middle Aged, Multiple Myeloma, Mutation, Plasma Cells, 25-Hydroxyvitamin D3 1-alpha-Hydroxylase, Tumor Suppressor Protein p53, Proto-Oncogene Proteins p21(ras), Sequence Analysis, DNA, Disease Progression, Mitogen-Activated Protein Kinases, Proto-Oncogene Proteins B-raf, Cyclin-Dependent Kinase Inhibitor p18, STAT3 Transcription Factor

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