title: Detection and prognostic value of recurrent exportin 1 mutations in tumor and cell-free circulating DNA of patients with classical Hodgkin lymphoma.
abstract: Classical Hodgkin lymphoma is one of the most common lymphomas and shares clinical and genetic features with primary mediastinal B-cell lymphoma. In this retrospective study, we analyzed the recurrent hotspot mutation of the exportin 1 (XPO1, p.E571K) gene, previously identified in primary mediastinal B-cell lymphoma, in biopsies and plasma circulating cell-free DNA from patients with classical Hodgkin lymphoma using a highly sensitive digital PCR technique. A total of 94 patients were included in the present study. This widely expressed XPO1 E571K mutation is present in one quarter of classical Hodgkin lymphoma patients (24.2%). Mutated and wild-type classical Hodgkin lymphomas were similar regarding the main clinical features. Patients with a detectable XPO1 mutation at the end of treatment displayed a tendency toward shorter progression-free survival, as compared to patients with undetectable mutation in plasma cell-free DNA (2-year progression-free survival: 57.1%, 95% confidence interval: 30.1-100% versus 2-year progression-free survival: 90.5%, 95% confidence interval: 78.8-100%, respectively, P=0.0601). To conclude, the detection of the XPO1 E571K mutation in biopsy and plasma cell-free DNA by digital PCR may be used as a novel biomarker in classical Hodgkin lymphoma for both diagnosis and minimal residual disease, and pinpoints a crucial role of XPO1 in classical Hodgkin lymphoma pathogenesis. The detection of somatic mutation in the plasma cell-free DNA of patients represents a major technological advance in the context of liquid biopsies and noninvasive management of classical Hodgkin lymphoma.
authors.affiliation: Department of Hematology, Centre Henri Becquerel, Rouen, France INSERM U918, Centre Henri Becquerel, University of Rouen, Rouen, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Camus
authors.affiliation: Department of Hematology, Centre Henri Becquerel, Rouen, France INSERM U918, Centre Henri Becquerel, University of Rouen, Rouen, France.
authors.forename: Aspasia
authors.initials: A
authors.lastname: Stamatoullas
authors.affiliation: INSERM U918, Centre Henri Becquerel, University of Rouen, Rouen, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Mareschal
authors.affiliation: INSERM U918, Centre Henri Becquerel, University of Rouen, Rouen, France.
authors.forename: Pierre-Julien
authors.initials: PJ
authors.lastname: Viailly
authors.affiliation: INSERM U1079, University of Rouen, Rouen, France.
authors.forename: Nasrin
authors.initials: N
authors.lastname: Sarafan-Vasseur
authors.affiliation: INSERM U918, Centre Henri Becquerel, University of Rouen, Rouen, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Bohers
authors.affiliation: INSERM U918, Centre Henri Becquerel, University of Rouen, Rouen, France.
authors.forename: Sydney
authors.initials: S
authors.lastname: Dubois
authors.affiliation: INSERM U918, Centre Henri Becquerel, University of Rouen, Rouen, France Department of Pathology, Centre Henri Becquerel, Rouen, France.
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Picquenot
authors.affiliation: INSERM U918, Centre Henri Becquerel, University of Rouen, Rouen, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ruminy
authors.affiliation: INSERM U918, Centre Henri Becquerel, University of Rouen, Rouen, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Maingonnat
authors.affiliation: INSERM U918, Centre Henri Becquerel, University of Rouen, Rouen, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bertrand
authors.affiliation: Department of Pathology, Centre Henri Becquerel, Rouen, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Cornic
authors.affiliation: Clinical Research Unit, Centre Henri Becquerel, Rouen, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Tallon-Simon
authors.affiliation: Department of Nuclear Medicine and Radiology, Centre Henri Becquerel and QuantIF (Litis EA4108 - FR CNRS 3638), Rouen, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Becker
authors.affiliation: Department of Pathology, Centre Henri Becquerel, Rouen, France.
authors.forename: Liana
authors.initials: L
authors.lastname: Veresezan
authors.affiliation: INSERM U1079, University of Rouen, Rouen, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Frebourg
authors.affiliation: Department of Nuclear Medicine and Radiology, Centre Henri Becquerel and QuantIF (Litis EA4108 - FR CNRS 3638), Rouen, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Vera
authors.affiliation: INSERM U918, Centre Henri Becquerel, University of Rouen, Rouen, France Department of Genetic Oncology, Centre Henri Becquerel, Rouen, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Bastard
authors.affiliation: Department of Hematology, Centre Henri Becquerel, Rouen, France INSERM U918, Centre Henri Becquerel, University of Rouen, Rouen, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Tilly
authors.affiliation: Department of Hematology, Centre Henri Becquerel, Rouen, France INSERM U918, Centre Henri Becquerel, University of Rouen, Rouen, France fabrice.jardin@chb.unicancer.fr.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Jardin
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D003062:Codon; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006689:Hodgkin Disease / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D006801:Humans; D028884:Karyopherins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D000072078:Positron Emission Tomography Computed Tomography; D011379:Prognosis; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D012008:Recurrence; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D047368:Tumor Burden; D055815:Young Adult; D000097606:Exportin 1 Protein
chemical_list: D014408:Biomarkers, Tumor; D003062:Codon; D004273:DNA, Neoplasm; D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein