Cell Reports (Apr 2017)
The Mutational Landscape of Circulating Tumor Cells in Multiple Myeloma
- Yuji Mishima,
- Bruno Paiva,
- Jiantao Shi,
- Jihye Park,
- Salomon Manier,
- Satoshi Takagi,
- Mira Massoud,
- Adriana Perilla-Glen,
- Yosra Aljawai,
- Daisy Huynh,
- Aldo M. Roccaro,
- Antonio Sacco,
- Marzia Capelletti,
- Alexandre Detappe,
- Diego Alignani,
- Kenneth C. Anderson,
- Nikhil C. Munshi,
- Felipe Prosper,
- Jens G. Lohr,
- Gavin Ha,
- Samuel S. Freeman,
- Eliezer M. Van Allen,
- Viktor A. Adalsteinsson,
- Franziska Michor,
- Jesus F. San Miguel,
- Irene M. Ghobrial
Affiliations
- Yuji Mishima
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Bruno Paiva
- Clinica Universidad de Navarra, Centro de Investigaciones Medicas Aplicadas (CIMA), Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona 31008, Spain
- Jiantao Shi
- Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
- Jihye Park
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Salomon Manier
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Satoshi Takagi
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Mira Massoud
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Adriana Perilla-Glen
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Yosra Aljawai
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Daisy Huynh
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Aldo M. Roccaro
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Antonio Sacco
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Marzia Capelletti
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Alexandre Detappe
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Diego Alignani
- Clinica Universidad de Navarra, Centro de Investigaciones Medicas Aplicadas (CIMA), Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona 31008, Spain
- Kenneth C. Anderson
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Nikhil C. Munshi
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Felipe Prosper
- Clinica Universidad de Navarra, Centro de Investigaciones Medicas Aplicadas (CIMA), Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona 31008, Spain
- Jens G. Lohr
- The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Gavin Ha
- The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Samuel S. Freeman
- The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Eliezer M. Van Allen
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Viktor A. Adalsteinsson
- The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Franziska Michor
- Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
- Jesus F. San Miguel
- Clinica Universidad de Navarra, Centro de Investigaciones Medicas Aplicadas (CIMA), Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona 31008, Spain
- Irene M. Ghobrial
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- DOI
- https://doi.org/10.1016/j.celrep.2017.03.025
- Journal volume & issue
-
Vol. 19,
no. 1
pp. 218 – 224
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.
