title: Digital PCR for quantification of recurrent and potentially actionable somatic mutations in circulating free DNA from patients with diffuse large B-cell lymphoma.
abstract: Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous malignancy harboring frequent targetable activating somatic mutations. Emerging evidence suggests that circulating cell-free DNA (cfDNA) can be used to detect somatic variants in DLBCL using Next-Generation Sequencing (NGS) experiments. In this proof-of-concept study, we chose to develop simple and valuable digital PCR (dPCR) assays for the detection of recurrent exportin-1 (XPO1) E571K, EZH2 Y641N, and MYD88 L265P mutations in DLBCL patients, thereby identifying patients most likely to potentially benefit from targeted therapies. We demonstrated that our dPCR assays were sufficiently sensitive to detect rare XPO1, EZH2, and MYD88 mutations in plasma cfDNA, with a sensitivity of 0.05%. cfDNA somatic mutation detection by dPCR seems to be a promising technique in the management of DLBCL, in addition to NGS experiments.
authors.affiliation: a Department of Hematology , Centre Henri Becquerel , Rouen , France ;|b INSERM U918, Centre Henri Becquerel, University of Rouen , Rouen , France ;
authors.forename: Vincent
authors.initials: V
authors.lastname: Camus
authors.affiliation: c INSERM U1079, University of Rouen , Rouen , France ;
authors.forename: Nasrin
authors.initials: N
authors.lastname: Sarafan-Vasseur
authors.affiliation: b INSERM U918, Centre Henri Becquerel, University of Rouen , Rouen , France ;
authors.forename: Elodie
authors.initials: E
authors.lastname: Bohers
authors.affiliation: b INSERM U918, Centre Henri Becquerel, University of Rouen , Rouen , France ;
authors.forename: Sydney
authors.initials: S
authors.lastname: Dubois
authors.affiliation: b INSERM U918, Centre Henri Becquerel, University of Rouen , Rouen , France ;
authors.forename: Sylvain
authors.initials: S
authors.lastname: Mareschal
authors.affiliation: b INSERM U918, Centre Henri Becquerel, University of Rouen , Rouen , France ;
authors.forename: Philippe
authors.initials: P
authors.lastname: Bertrand
authors.affiliation: b INSERM U918, Centre Henri Becquerel, University of Rouen , Rouen , France ;
authors.forename: Pierre-Julien
authors.initials: PJ
authors.lastname: Viailly
authors.affiliation: b INSERM U918, Centre Henri Becquerel, University of Rouen , Rouen , France ;
authors.forename: Philippe
authors.initials: P
authors.lastname: Ruminy
authors.affiliation: b INSERM U918, Centre Henri Becquerel, University of Rouen , Rouen , France ;
authors.forename: Catherine
authors.initials: C
authors.lastname: Maingonnat
authors.affiliation: a Department of Hematology , Centre Henri Becquerel , Rouen , France ;|b INSERM U918, Centre Henri Becquerel, University of Rouen , Rouen , France ;
authors.forename: Emilie
authors.initials: E
authors.lastname: Lemasle
authors.affiliation: a Department of Hematology , Centre Henri Becquerel , Rouen , France ;|b INSERM U918, Centre Henri Becquerel, University of Rouen , Rouen , France ;
authors.forename: Aspasia
authors.initials: A
authors.lastname: Stamatoullas
authors.affiliation: d Department of Pathology , Centre Henri Becquerel , Rouen , France ;
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Picquenot
authors.affiliation: d Department of Pathology , Centre Henri Becquerel , Rouen , France ;
authors.forename: Marie
authors.initials: M
authors.lastname: Cornic
authors.affiliation: c INSERM U1079, University of Rouen , Rouen , France ;
authors.forename: Ludivine
authors.initials: L
authors.lastname: Beaussire
authors.affiliation: b INSERM U918, Centre Henri Becquerel, University of Rouen , Rouen , France ;|e Department of Genetic Oncology , Centre Henri Becquerel , Rouen , France.
authors.forename: Christian
authors.initials: C
authors.lastname: Bastard
authors.affiliation: c INSERM U1079, University of Rouen , Rouen , France ;
authors.forename: Thierry
authors.initials: T
authors.lastname: Frebourg
authors.affiliation: a Department of Hematology , Centre Henri Becquerel , Rouen , France ;|b INSERM U918, Centre Henri Becquerel, University of Rouen , Rouen , France ;
authors.forename: Hervé
authors.initials: H
authors.lastname: Tilly
authors.affiliation: a Department of Hematology , Centre Henri Becquerel , Rouen , France ;|b INSERM U918, Centre Henri Becquerel, University of Rouen , Rouen , France ;
authors.forename: Fabrice
authors.initials: F
authors.lastname: Jardin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D028884:Karyopherins / Q000235:genetics; D000073890:Liquid Biopsy; D016403:Lymphoma, Large B-Cell, Diffuse / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography; D060888:Real-Time Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D012008:Recurrence; D000097606:Exportin 1 Protein
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D028884:Karyopherins; D053594:Myeloid Differentiation Factor 88; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein; C507779:MYD88 protein, human
keywords: Circulating DNA; DLBCL; digital PCR; exportin-1; somatic mutations