title: Relevance of ID3-TCF3-CCND3 pathway mutations in pediatric aggressive B-cell lymphoma treated according to the non-Hodgkin Lymphoma Berlin-Frankfurt-Münster protocols.
abstract: Mature B-cell non-Hodgkin lymphoma is the most common subtype of non-Hodgkin lymphoma in childhood and adolescence. B-cell non-Hodgkin lymphomas 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 theMYConcogene are known as relevant but not sufficient 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, TCF3andCCND3are potential drivers of Burkitt lymphomagenesis. In the study herein, frequency and clinical relevance of mutations inID3, TCF3andCCND3were analyzed within a well-defined cohort of 84 uniformly diagnosed and treated pediatric B-cell non-Hodgkin lymphoma patients of the Berlin-Frankfurt-Münster group. Mutation frequency was 78% (ID3), 13% (TCF3) and 36% (CCND3) in Burkitt lymphoma (including Burkitt leukemia).ID3andCCND3mutations were associated with more advanced stages of the disease inMYCrearrangement positive Burkitt lymphoma. In conclusion,ID3-TCF3-CCND3pathway genes are mutated in more than 88% ofMYC-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.
authors.affiliation: Department of Pediatric Hematology and Oncology, Justus-Liebig-University Giessen, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Rohde
authors.affiliation: Department of Pediatric Hematology and Oncology, Justus-Liebig-University Giessen, Germany.
authors.forename: Bettina R
authors.initials: BR
authors.lastname: Bonn
authors.affiliation: Department of Pediatric Hematology and Oncology, Justus-Liebig-University Giessen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.affiliation: Pediatric Hematology and Oncology, University Hospital Münster, Germany.|Translational Oncology, Department of Medicine A, University Hospital Münster; Cluster of Excellence EXC 1003, Cells in Motion, Münster, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Lange
authors.affiliation: Pediatric Hematology and Oncology, University Medical Center Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Möricke
authors.affiliation: Department of Pathology, Hematopathology Section and Lymph Node Registry, University Hospital Schleswig-Holstein, Campus Kiel/Christian-Albrecht University, Kiel, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.affiliation: Department of Pathology, Hematopathology Section and Lymph Node Registry, University Hospital Schleswig-Holstein, Campus Kiel/Christian-Albrecht University, Kiel, Germany.
authors.forename: Ilske
authors.initials: I
authors.lastname: Oschlies
authors.affiliation: Department of Pathology, Hematopathology Section and Lymph Node Registry, University Hospital Schleswig-Holstein, Campus Kiel/Christian-Albrecht University, Kiel, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Szczepanowski
authors.affiliation: Institute of Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Nagel
authors.affiliation: Pediatric Hematology and Oncology, University Medical Center Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
authors.affiliation: Institute for Medical Informatics Statistics and Epidemiology, University Leipzig, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Loeffler
authors.affiliation: Institute of Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Germany.|Institute of Human Genetics, University of Ulm and University Medical Center Ulm, Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.affiliation: Department of Pediatric Hematology and Oncology, Justus-Liebig-University Giessen, Germany.
authors.forename: Alfred
authors.initials: A
authors.lastname: Reiter
authors.affiliation: Pediatric Hematology and Oncology, University Hospital Münster, Germany birgit.burkhardt@ukmuenster.de.
authors.forename: Birgit
authors.initials: B
authors.lastname: Burkhardt
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002051:Burkitt Lymphoma / Q000235:genetics; D002648:Child; D056743:Cyclin D3 / Q000378:metabolism; D005260:Female; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000628:therapy; D008297:Male; D059645:Mutation Rate; D009363:Neoplasm Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D056743:Cyclin D3; D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; C534696:CCND3 protein, human; C407909:TCF3 protein, human; C075640:ID3 protein, human