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

S. Manier, J. Park, M. Capelletti, M. Bustoros, S. S. Freeman, G. Ha, J. Rhoades, C. J. Liu, D. Huynh, S. C. Reed, G. Gydush, K. Z. Salem, D. Rotem, C. Freymond, A. Yosef, A. Perilla-Glen, L. Garderet, E. M. Van Allen, Shaji K Kumar, J. C. LoveG. Getz, V. A. Adalsteinsson, I. M. Ghobrial

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number1691
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

Exome
Circulating Neoplastic Cells
sequencing
Multiple Myeloma
Tumors
tumors
deoxyribonucleic acid
Cells
DNA
cells
Neoplasms
Biopsy
mutations
Mutation
Precision Medicine
blood
Blood
cancer
Disease Progression
genome

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Manier, S., Park, J., Capelletti, M., Bustoros, M., Freeman, S. S., Ha, G., ... Ghobrial, I. M. (2018). Whole-exome sequencing of cell-free DNA and circulating tumor cells in multiple myeloma. Nature Communications, 9(1), [1691]. https://doi.org/10.1038/s41467-018-04001-5

Whole-exome sequencing of cell-free DNA and circulating tumor cells in multiple myeloma. / Manier, S.; Park, J.; Capelletti, M.; Bustoros, M.; Freeman, S. S.; Ha, G.; Rhoades, J.; Liu, C. J.; Huynh, D.; Reed, S. C.; Gydush, G.; Salem, K. Z.; Rotem, D.; Freymond, C.; Yosef, A.; Perilla-Glen, A.; Garderet, L.; Van Allen, E. M.; Kumar, Shaji K; Love, J. C.; Getz, G.; Adalsteinsson, V. A.; Ghobrial, I. M.

In: Nature Communications, Vol. 9, No. 1, 1691, 01.12.2018.

Research output: Contribution to journalArticle

Manier, S, Park, J, Capelletti, M, Bustoros, M, Freeman, SS, Ha, G, Rhoades, J, Liu, CJ, Huynh, D, Reed, SC, Gydush, G, Salem, KZ, Rotem, D, Freymond, C, Yosef, A, Perilla-Glen, A, Garderet, L, Van Allen, EM, Kumar, SK, Love, JC, Getz, G, Adalsteinsson, VA & Ghobrial, IM 2018, 'Whole-exome sequencing of cell-free DNA and circulating tumor cells in multiple myeloma', Nature Communications, vol. 9, no. 1, 1691. https://doi.org/10.1038/s41467-018-04001-5
Manier, S. ; Park, J. ; Capelletti, M. ; Bustoros, M. ; Freeman, S. S. ; Ha, G. ; Rhoades, J. ; Liu, C. J. ; Huynh, D. ; Reed, S. C. ; Gydush, G. ; Salem, K. Z. ; Rotem, D. ; Freymond, C. ; Yosef, A. ; Perilla-Glen, A. ; Garderet, L. ; Van Allen, E. M. ; Kumar, Shaji K ; Love, J. C. ; Getz, G. ; Adalsteinsson, V. A. ; Ghobrial, I. M. / Whole-exome sequencing of cell-free DNA and circulating tumor cells in multiple myeloma. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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