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, T. Buzder, G. Molnar, M. Zangari, F. Rhee, S. Thanendrarajan, C. Schinke, J. Epstein, F. E. Davies, B. A. Walker, T. Meissner, B. Barlogie, G. J. Morgan and N. Weinhold ()
Additional contact information
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

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: 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.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-017-00296-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00296-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-00296-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().