Whole-exome sequencing of cell-free DNA and circulating tumor cells in multiple myeloma

Nat Commun. 2018 Apr 27;9(1):1691. doi: 10.1038/s41467-018-04001-5.


Liquid biopsies including circulating tumor cells (CTCs) and cell-free DNA (cfDNA) have enabled minimally invasive characterization of many cancers, but are rarely analyzed together. Understanding the detectability and genomic concordance of CTCs and cfDNA may inform their use in guiding cancer precision medicine. Here, we report the detectability of cfDNA and CTCs in blood samples from 107 and 56 patients with multiple myeloma (MM), respectively. Using ultra-low pass whole-genome sequencing, we find both tumor fractions correlate with disease progression. Applying whole-exome sequencing (WES) to cfDNA, CTCs, and matched tumor biopsies, we find concordance in clonal somatic mutations (~99%) and copy number alterations (~81%) between liquid and tumor biopsies. Importantly, analyzing CTCs and cfDNA together enables cross-validation of mutations, uncovers mutations exclusive to either CTCs or cfDNA, and allows blood-based tumor profiling in a greater fraction of patients. Our study demonstrates the utility of analyzing both CTCs and cfDNA in MM.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Bone Marrow / pathology
  • Circulating Tumor DNA / genetics*
  • DNA Copy Number Variations / genetics
  • Disease Progression
  • Female
  • Humans
  • Liquid Biopsy / methods
  • Male
  • Middle Aged
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / pathology
  • Mutation / genetics
  • Neoplastic Cells, Circulating*
  • Precision Medicine / methods
  • Whole Exome Sequencing / methods*


  • Biomarkers, Tumor
  • Circulating Tumor DNA