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Ferrata Storti Foundation
Haematologica 2018 Volume 104(2):330-337
Non-Hodgkin Lymphoma
JUNB, DUSP2, SGK1, SOCS1 and CREBBP are frequently mutated in T-cell/histiocyte- rich large B-cell lymphoma
Bianca Schuhmacher,1 Julia Bein,1 Tobias Rausch,2,3 Vladimir Benes2, Thomas Tousseyn,4 Martine Vornanen,5 Maurilio Ponzoni,6 Lorenz Thurner,7,8 Randy Gascoyne,9 Christian Steidl,9 Ralf Küppers,10,11 Martin-Leo Hansmann1,12,13 and Sylvia Hartmann1,12
1Dr. Senckenberg Institute of Pathology, Goethe University, Frankfurt am Main, Germany; 2Genecore, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany; 3Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany; 4Department of Pathology, University Hospitals K.U.Leuven, Belgium; 5Department of Pathology, Tampere University Hospital and University of Tampere, Finland; 6Unit of Lymphoid Malignancies, Department of Pathology, Scientific Institute San Raffaele, Milan, Italy; 7José Carreras Center for Immuno and Gene Therapy and Internal Medicine I, Saarland University Medical School, Homburg, Saar, Germany; 8Department of Internal Medicine 2, Hospital of the J. W. Goethe University, Frankfurt am Main, Germany; 9Department of Pathology and Laboratory Medicine and the Centre for Lymphoid Cancer, British Columbia Cancer Agency, University of British Columbia, Vancouver, Canada; 10Institute of Cell Biology (Cancer Research), Faculty of Medicine, University of Duisburg- Essen, Essen, Germany; 11Deutsches Konsortium für Translationale Krebsforschung (DKTK), Germany; 12Reference and Consultant Center for Lymphoma and Lymph Node Diagnostics, Goethe University, Frankfurt am Main, Germany and 13Frankfurt Institute of Advanced Studies, Frankfurt am Main, Germany
ABSTRACT
T-cell/histiocyte-rich large B-cell lymphoma is a rare aggressive lymphoma showing histopathological overlap with nodular lym- phocyte-predominant Hodgkin lymphoma. Despite differences in tumor microenvironment and clinical behavior, the tumor cells of both entities show remarkable similarities, suggesting that both lymphomas might represent a spectrum of the same disease. To address this issue, we investigated whether these entities share mutations. Ultra-deep tar- geted resequencing of six typical and 11 histopathological variants of nodular lymphocyte-predominant Hodgkin lymphoma, and nine cases of T-cell/histiocyte-rich large B-cell lymphoma revealed that genes recur- rently mutated in nodular lymphocyte-predominant Hodgkin lym- phoma are affected by mutations at similar frequencies in T-cell/histio- cyte-rich large B-cell lymphoma. The most recurrently mutated genes were JUNB, DUSP2, SGK1, SOCS1 and CREBBP, which harbored muta- tions more frequently in T-cell/histiocyte-rich large B-cell lymphoma and the histopathological variants of nodular lymphocyte-predominant Hodgkin lymphoma than in its typical form. Mutations in JUNB, DUSP2, SGK1 and SOCS1 were highly enriched for somatic hypermu- tation hotspot sites, suggesting an important role of aberrant somatic hypermutation in the generation of these somatic mutations and thus in the pathogenesis of both lymphoma entities. Mutations in JUNB are generally rarely observed in malignant lymphomas and thus are relative- ly specific for nodular lymphocyte-predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma at such high frequencies (5/17 and 5/9 cases with JUNB mutations, respectively). Taken together, the findings of the present study further support a close relationship between T-cell/histiocyte-rich large B-cell lymphoma and nodular lym- phocyte-predominant Hodgkin lymphoma by showing that they share highly recurrent genetic lesions.
Correspondence:
s.hartmann@em.uni-frankfurt.de
Received: August 1, 2018. Accepted: September 7, 2018. Pre-published: September 13, 2018.
doi:10.3324/haematol.2018.203224
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/2/330
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