The Mutational Landscape of Circulating Tumor Cells in Multiple Myeloma

Cell Rep. 2017 Apr 4;19(1):218-224. doi: 10.1016/j.celrep.2017.03.025.

Abstract

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.

Publication types

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

MeSH terms

  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Bone Marrow Neoplasms / blood
  • Bone Marrow Neoplasms / genetics*
  • Bone Marrow Neoplasms / pathology
  • Cell Count
  • DNA / blood
  • DNA Mutational Analysis
  • Exome Sequencing
  • GTP Phosphohydrolases / blood
  • GTP Phosphohydrolases / genetics
  • Genetic Testing / methods*
  • Humans
  • Longitudinal Studies
  • Membrane Proteins / blood
  • Membrane Proteins / genetics
  • Middle Aged
  • Multiple Myeloma / blood
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / pathology
  • Mutation
  • Neoplastic Cells, Circulating*
  • Prognosis
  • Proto-Oncogene Proteins B-raf / blood
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras) / blood
  • Proto-Oncogene Proteins p21(ras) / genetics

Substances

  • Biomarkers, Tumor
  • KRAS protein, human
  • Membrane Proteins
  • DNA
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • GTP Phosphohydrolases
  • NRAS protein, human
  • Proto-Oncogene Proteins p21(ras)