Evidence map›Paper›PMID 28814763›Full record

ArticleNature communications2017

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

L Rasche, S S Chavan, O W Stephens, P H Patel, R Tytarenko, C Ashby, M Bauer, C Stein, S Deshpande, C Wardell and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 263 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
263citing papers in PubMed, 3 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

263 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. EANM guidelines on the use of [European journal of nuclear medicine and molecular imaging · 2024
    Guideline
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  9. Imaging B cell maturation antigen in multiple myeloma.The Journal of clinical investigation · 2026
    Article
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203 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

L RascheMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
S S ChavanMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
O W StephensMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
P H PatelMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
R TytarenkoMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
C AshbyMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
M BauerMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.ORCID http://orcid.org/0000-0003-2498-7295
C SteinMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
S DeshpandeMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
C WardellMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
T BuzderMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
G MolnarMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
M ZangariMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
F van RheeMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
S ThanendrarajanMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
C SchinkeMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
J EpsteinMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
F E DaviesMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
B A WalkerMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.ORCID http://orcid.org/0000-0002-8615-6254
T MeissnerDepartment of Molecular and Experimental Medicine, Avera Cancer Institute, Sioux Falls, SD, 57105, USA.
B BarlogieMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
G J MorganMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
N WeinholdMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA. NWeinhold@uams.edu.

Funding

Tumor Cell-Microenvironment Interactions in the Molecular Pathogenesis of MultiplP01CA055819 · NCI · UNIV OF ARKANSAS FOR MED SCIS · PI BELLAMY, WILLIAM T · 1993 to 2013
$49.7M
NCI NIH HHS P01 CA055819
6 · The paper itself

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.In multiple myeloma, malignant cells expand within bone marrow. Here, the authors use multi-region sequencing in patient samples to analyse spatial clonal architecture and heterogeneity, providing novel insight into multiple myeloma progression and evolution.

Indexed as

25-Hydroxyvitamin D3 1-alpha-HydroxylaseAgedAged, 80 and overBone MarrowCyclin-Dependent Kinase Inhibitor p18Disease ProgressionFemaleFibroblast Growth FactorsHumansMaleMiddle AgedMitogen-Activated Protein KinasesMultiple MyelomaMutationPlasma CellsProto-Oncogene Proteins B-raf25-Hydroxyvitamin D3 1-alpha-HydroxylaseBRAF protein, humanCDKN2C protein, humanCyclin-Dependent Kinase Inhibitor p18CYP27B1 protein, humanFGF12 protein, humanFibroblast Growth FactorsKRAS protein, humanMitogen-Activated Protein KinasesProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)STAT3 protein, humanSTAT3 Transcription FactorTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID28814763
PMCPMC5559527

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.