Sylvain Mareschal, Ph.D.
Bioinformatics engineer
June 13, 2016 at 19:30
Camus et al, Haematologica 2016
Haematologica. 2016 Sep;101(9):1094-101.
doi: 10.3324/haematol.2016.145102.
Epub 2016 Jun 13.

Detection and prognostic value of recurrent XPO1 mutations in tumor and cell-free circulating DNA of patients with classical Hodgkin Lymphoma.

Camus V, Stamatoullas A, Mareschal S, Viailly PJ, Sarafan-Vasseur N, Bohers E, Dubois S, Picquenot JM, Ruminy P, Maingonnat C, Bertrand P, Cornic M, Tallon-Simon V, Becker S, Veresezan L, Frebourg T, Vera P, Bastard C, Tilly H, Jardin F.

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 negative patients (2-years progression free-survival: 57.1%, 95% confidence interval: 30.1%-100% versus 2-years 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.

Pubmed, PMID: 27479820