Spatial genomic heterogeneity in multiple myeloma revealed by multi-region sequencing.
IF: 17.694
Cited by: 239


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.


Spatial Genomics

MeSH terms

25-Hydroxyvitamin D3 1-alpha-Hydroxylase
Aged, 80 and over
Bone Marrow
Cyclin-Dependent Kinase Inhibitor p18
Disease Progression
Fibroblast Growth Factors
Middle Aged
Mitogen-Activated Protein Kinases
Multiple Myeloma
Plasma Cells
Proto-Oncogene Proteins B-raf
Proto-Oncogene Proteins p21(ras)
STAT3 Transcription Factor
Sequence Analysis, DNA
Tumor Suppressor Protein p53


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

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