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Haematologica. 2016 Sep;101(9):1094-101. doi: 10.3324/haematol.2016.145102. Epub 2016 Jun 13.

Detection and prognostic value of recurrent exportin 1 mutations in tumor and cell-free circulating DNA of patients with classical Hodgkin lymphoma.

Author information

1
Department of Hematology, Centre Henri Becquerel, Rouen, France INSERM U918, Centre Henri Becquerel, University of Rouen, Rouen, France.
2
INSERM U918, Centre Henri Becquerel, University of Rouen, Rouen, France.
3
INSERM U1079, University of Rouen, Rouen, France.
4
INSERM U918, Centre Henri Becquerel, University of Rouen, Rouen, France Department of Pathology, Centre Henri Becquerel, Rouen, France.
5
Department of Pathology, Centre Henri Becquerel, Rouen, France.
6
Clinical Research Unit, Centre Henri Becquerel, Rouen, France.
7
Department of Nuclear Medicine and Radiology, Centre Henri Becquerel and QuantIF (Litis EA4108 - FR CNRS 3638), Rouen, France.
8
INSERM U918, Centre Henri Becquerel, University of Rouen, Rouen, France Department of Genetic Oncology, Centre Henri Becquerel, Rouen, France.
9
Department of Hematology, Centre Henri Becquerel, Rouen, France INSERM U918, Centre Henri Becquerel, University of Rouen, Rouen, France fabrice.jardin@chb.unicancer.fr.

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.

PMID:
27479820
PMCID:
PMC5060026
DOI:
10.3324/haematol.2016.145102
[Indexed for MEDLINE]
Free PMC Article

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