The Mutational Landscape of Circulating Tumor Cells in Multiple Myeloma

The development of sensitive and non-invasive “liquid biopsies” presents new opportunities for longitudinal monitoring of tumor dissemination and clonal evolution. The number of circulating tumor cells (CTCs) is prognostic in multiple myeloma (MM), but there is little information on their genetic features. Here, we have analyzed the genomic landscape of CTCs from 29 MM patients, including eight cases with matched/paired bone marrow (BM) tumor cells. Our results show that 100% of clonal mutations in patient BM were detected in CTCs and that 99% of clonal mutations in CTCs were present in BM MM. These include typical driver mutations in MM such as in KRAS, NRAS, or BRAF. These data suggest that BM and CTC samples have similar clonal structures, as discordances between the two were restricted to subclonal mutations. Accordingly, our results pave the way for potentially less invasive mutation screening of MM patients through characterization of CTCs. [Display omitted] •MM patient-derived CTCs mirror the mutational profile obtained from BM biopsy•Somatic copy-number alteration of CTCs was highly concordant with paired BM tumors•We suggest roles for CTCs in the prognostic and molecular profiling of MM patients Mishima et al. perform genomic analysis of circulating tumor cells of patients with multiple myeloma and find that circulating tumor cells have similar clonal and sub-clonal structures with matched bone marrow clonal plasma cells. This study defines a role for CTCs in the molecular profiling of multiple myeloma patients.