- 1 Department of Pediatric Hematology and Oncology, Justus-Liebig-University Giessen, Giessen, Germany;
- 2 Pediatric Hematology and Oncology, University Hospital Muenster, Muenster, Germany;
- 3 Pediatric Hematology and Oncology, University Medical Center Schleswig-Holstein, Kiel, Germany;
- 4 Dept. of Pathology, Hematopathology Section and Lymph Node Registry, University Kiel, Kiel, Germany;
- 5 Institute of Human Genetics, Christian-Albrechts-University Kiel, Kiel, Germany;
- 6 Institute for Medical Informatics Statistics and Epidemiology, University Leipzig, Leipzig, Germany;
- 7 Institute of Human Genetics, University of Ulm and Medical Center Ulm, Ulm, Germany
- ↵* Corresponding author; email:
Mature B-cell Non-Hodgkin lymphoma is the most common subtype of Non-Hodgkin lymphoma in childhood and adolescence. B-cell Non-Hodgkin lymphoma are further classified into histological subtypes, with Burkitt lymphoma and Diffuse large B-cell lymphoma being the most common subgroups in pediatric patients. Translocations involving the MYC oncogene are known as relevant but not sufficient hit for Burkitt lymphoma pathogenesis. Recently published large-scale next-generation sequencing studies unveiled sets of additional recurrently mutated genes in samples of pediatric and adult B-cell Non-Hodgkin lymphoma patients. ID3, TCF3 and CCND3 are potential drivers of Burkitt-lymphomagenesis. In the present study frequency and clinical relevance of mutations in ID3, TCF3 and CCND3 were analyzed within a well-defined cohort of 84 uniformly diagnosed and treated pediatric B-cell Non-Hodgkin lymphoma patients of the Berlin-Frankfurt-Munster group (NHL-BFM). Mutation frequency was 78% (ID3), 13% (TCF3) and 36% (CCND3) in Burkitt lymphoma (including Burkitt leukemia). ID3 and CCND3 mutations were associated with more advanced stages of the disease in MYC rearrangement positive Burkitt lymphoma. In conclusion ID3-TCF3-CCND3 pathway genes are mutated in more than 88% of MYC-rearranged pediatric B-cell Non-Hodgkin lymphoma and the pathway may represent a highly relevant second hit of Burkitt lymphoma pathogenesis especially in children and adolescents.
ICGC-MMML-Seq: Gesine Richter, Reiner Siebert, Susanne Wagner, Andrea Haake, Julia Richter, Roland Eils, Chris Lawerenz, Sylwester Radomski, Ingrid Scholz, Anke Bergmann, Christoph Borst, Birgit Burkhardt, Alexander Claviez, Martin Dreyling, Sonja Eberth, Hermann Einsele, Norbert Frickhofen, Siegfried Haas, Martin-Leo Hansmann, Dennis Karsch, Michael Kneba, Jasmin Lisfeld, Luisa Mantovani-Löffler, Christina Stadler, Peter Staib, Stephan Stilgenbauer, German Ott, Lorenz Trümper, Thorsen Zenz, Dieter Kube, Ralf Küppers, Marc Weniger, Michael Hummel, Wolfram Klapper, Ulrike Kostezka, Dido Lenze, Peter Möller, Andreas Rosenwald, Monika Szczepanowski, Ole Ammerpohl, Sietse Aukema, Vera Binder, Arndt Borkhardt, Kebria Hezaveh, Jessica Hoell, Ellen Leich, Peter Lichter, Christina Lopez, Inga Nagel, Jordan Pischimariov, Bernhard Radlwimmer, Philip Rosenstiel, Markus Schilhabel, Stefan Schreiber, Inga Vater, Rabea Wagner, Stephan H. Bernhart, Hans Binder, Benedikt Brors, Gero Doose, Jürgen Eils, Steve Hoffmann, Lydia Hopp, Helene Kretzmer, Markus Kreuz, Jan Korbel, David Langenberger, Markus Loeffler, Maciej Rosolowski, Matthias Schlesner, Peter F. Stadler, Stefanie Sungalee
MMML-MYC-SYS: Sietse Aukema, Arndt Borkhardt, Birgit Burkhardt, Nina Habermann, Jessica Hoell, Jan Korbel, Jonas Lange, Inga Nagel, Reiner Siebert, Stefanie Sungalee, Michael Altenbuchinger, Katja Dettmer-Wilde, Lora Dimitrova, Julia Engelmann, Maren Feist, Wolfram Gronwald, Michael Hummel, Karsten Kleo, Dieter Kube, Peter Oefner, Phillip Schwarzfischer, Reiner Spang, Franziska Taruttis, Wolfram Klapper, Monika Szczepanowski, Lorenz Trümper, Hans Binder, Matthias Horn, Markus Kreuz, Henry Löffler-Wirth
- Received September 27, 2016.
- Accepted February 7, 2017.
- Copyright © 2017, Ferrata Storti Foundation