Genetic interrogation of circulating multiple myeloma cells at single-cell resolution.

Sci Transl Med
Authors
Keywords
Abstract

Multiple myeloma (MM) remains an incurable disease, with a treatment-refractory state eventually developing in all patients. Constant clonal evolution and genetic heterogeneity of MM are a likely explanation for the emergence of drug-resistant disease. Monitoring of MM genomic evolution on therapy by serial bone marrow biopsy is unfortunately impractical because it involves an invasive and painful procedure. We describe how noninvasive and highly sensitive isolation and characterization of circulating tumor cells (CTCs) from peripheral blood at single-cell resolution recapitulate MM in the bone marrow. We demonstrate that CTCs provide the same genetic information as bone marrow MM cells and even reveal mutations with greater sensitivity than bone marrow biopsies in some cases. Single CTC RNA sequencing enables classification of MM and quantitative assessment of genes that are relevant for prognosis. We propose that the genomic characterization of CTCs should be included in clinical trials to follow the emergence of resistant subclones after MM therapy.

Year of Publication
2016
Journal
Sci Transl Med
Volume
8
Issue
363
Pages
363ra147
Date Published
2016 11 02
ISSN
1946-6242
DOI
10.1126/scitranslmed.aac7037
PubMed ID
27807282
PubMed Central ID
PMC5426804
Links
Grant list
K08 CA191026 / CA / NCI NIH HHS / United States
K08 CA191091 / CA / NCI NIH HHS / United States
HHMI / Howard Hughes Medical Institute / United States