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

Leo RascheMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USAShweta S. ChavanMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USAOwen StephensMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USAPragi PatelMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USARuslana G. TytarenkoMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USACody AshbyMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USAMichael BauerMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USAJoshua EpsteinMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USAS DeshpandeMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USAChristopher P. WardellMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USATímea BuzderMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USAGábor MolnárMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USAMaurizio ZangariMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USAFrits van RheeMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USASharmilan ThanendrarajanMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USACarolina SchinkeMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USAFaith E. DaviesMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USABrian A. WalkerMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USATobias MeißnerDepartment of Molecular and Experimental Medicine, Avera Cancer Institute, Sioux Falls, SD, 57105, USABart BarlogieMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USAGareth J. MorganMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USANiels WeinholdMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA

2017en

ABI

Annotatsiya

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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Identifikatorlar

DOI: 10.1038/s41467-017-00296-y

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