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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, S; Love, J C; Getz, G; Adalsteinsson, V A; Ghobrial, I M.
Affiliation
  • Manier S; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115, USA.
  • Park J; Hematology Department, CHU, Univ. Lille, 59000, Lille, France.
  • Capelletti M; INSERM UMR-S1172, 59000, Lille, France.
  • Bustoros M; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115, USA.
  • Freeman SS; Brigham and Women's Hospital, Boston, MA, 02115, USA.
  • Ha G; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115, USA.
  • Rhoades J; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115, USA.
  • Liu CJ; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
  • Huynh D; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
  • Reed SC; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
  • Gydush G; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115, USA.
  • Salem KZ; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115, USA.
  • Rotem D; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
  • Freymond C; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
  • Yosef A; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115, USA.
  • Perilla-Glen A; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
  • Garderet L; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115, USA.
  • Van Allen EM; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115, USA.
  • Kumar S; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115, USA.
  • Love JC; Department of Hematology, St-Antoine University Hospital, Paris, 75000, France.
  • Getz G; Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115, USA.
  • Adalsteinsson VA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
  • Ghobrial IM; Department of Hematology, Mayo Clinic, Rochester, MN, 55902, USA.
Nat Commun ; 9(1): 1691, 2018 04 27.
Article in En | MEDLINE | ID: mdl-29703982
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Biomarkers, Tumor / Circulating Tumor DNA / Exome Sequencing / Multiple Myeloma / Neoplastic Cells, Circulating Type of study: Evaluation_studies Limits: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2018 Document type: Article Affiliation country: Estados Unidos
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Biomarkers, Tumor / Circulating Tumor DNA / Exome Sequencing / Multiple Myeloma / Neoplastic Cells, Circulating Type of study: Evaluation_studies Limits: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2018 Document type: Article Affiliation country: Estados Unidos