The Mutational Landscape of Circulating Tumor Cells in Multiple Myeloma.

Fiche publication


Date publication

avril 2017

Journal

Cell reports

Auteurs

Membres identifiés du Cancéropôle Est :
Dr DETAPPE Alexandre


Tous les auteurs :
Mishima Y, Paiva B, Shi J, Park J, Manier S, Takagi S, Massoud M, Perilla-Glen A, Aljawai Y, Huynh D, Roccaro AM, Sacco A, Capelletti M, Detappe A, Alignani D, Anderson KC, Munshi NC, Prosper F, Lohr JG, Ha G, Freeman SS, Van Allen EM, Adalsteinsson VA, Michor F, San Miguel JF, Ghobrial IM

Résumé

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.

Mots clés

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

Référence

Cell Rep. 2017 04 4;19(1):218-224