title: The Mutational Landscape of Circulating Tumor Cells in Multiple Myeloma.
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.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mishima
authors.affiliation: Clinica Universidad de Navarra, Centro de Investigaciones Medicas Aplicadas (CIMA), Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona 31008, Spain.
authors.forename: Bruno
authors.initials: B
authors.lastname: Paiva
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA.
authors.forename: Jiantao
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Jihye
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Salomon
authors.initials: S
authors.lastname: Manier
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takagi
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Mira
authors.initials: M
authors.lastname: Massoud
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Adriana
authors.initials: A
authors.lastname: Perilla-Glen
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Yosra
authors.initials: Y
authors.lastname: Aljawai
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Daisy
authors.initials: D
authors.lastname: Huynh
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; ASST Spedali Civili Department Medical Oncology, CREA Laboratory, Brescia 25121, Italy.
authors.forename: Aldo M
authors.initials: AM
authors.lastname: Roccaro
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; ASST Spedali Civili Department Medical Oncology, CREA Laboratory, Brescia 25121, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Sacco
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Marzia
authors.initials: M
authors.lastname: Capelletti
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Detappe
authors.affiliation: Clinica Universidad de Navarra, Centro de Investigaciones Medicas Aplicadas (CIMA), Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona 31008, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Alignani
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Nikhil C
authors.initials: NC
authors.lastname: Munshi
authors.affiliation: Clinica Universidad de Navarra, Centro de Investigaciones Medicas Aplicadas (CIMA), Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona 31008, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: Prosper
authors.affiliation: The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Jens G
authors.initials: JG
authors.lastname: Lohr
authors.affiliation: The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Gavin
authors.initials: G
authors.lastname: Ha
authors.affiliation: The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Freeman
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Eliezer M
authors.initials: EM
authors.lastname: Van Allen
authors.affiliation: The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Viktor A
authors.initials: VA
authors.lastname: Adalsteinsson
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA.
authors.forename: Franziska
authors.initials: F
authors.lastname: Michor
authors.affiliation: Clinica Universidad de Navarra, Centro de Investigaciones Medicas Aplicadas (CIMA), Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona 31008, Spain.
authors.forename: Jesus F
authors.initials: JF
authors.lastname: San Miguel
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Electronic address: irene_ghobrial@dfci.harvard.edu.
authors.forename: Irene M
authors.initials: IM
authors.lastname: Ghobrial
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D019046:Bone Marrow Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D002452:Cell Count; D004247:DNA / Q000097:blood; D004252:DNA Mutational Analysis; D020558:GTP Phosphohydrolases / Q000097:blood / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008137:Longitudinal Studies; D008565:Membrane Proteins / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009360:Neoplastic Cells, Circulating; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000097:blood / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000097:blood / Q000235:genetics; D000073359:Exome Sequencing
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D008565:Membrane Proteins; D004247:DNA; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)