Recurrent loss of heterozygosity in 1p36 associated with TNFRSF14 mutations in IRF4 translocation negative pediatric follicular lymphomas
Idoia Martin-Guerrero,
Itziar Salaverria,
Birgit Burkhardt,
Monika Szczepanowski,
Michael Baudis,
Susanne Bens,
Laurence de Leval,
Africa Garcia-Orad,
Heike Horn,
Jasmin Lisfeld,
Shoji Pellissery,
Wolfram Klapper,
Ilske Oschlies,
Reiner Siebert
Affiliations
Idoia Martin-Guerrero
Institute of Human Genetics, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Kiel, Germany;Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country, UPV-EHU, Spain
Itziar Salaverria
Institute of Human Genetics, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Kiel, Germany
Birgit Burkhardt
NHL-BFM Study Center, Department of Pediatric Hematology and Oncology, Justus-Liebig-University, Giessen, Germany;Pediatric Hematology and Oncology, University Hospital Münster, Germany
Monika Szczepanowski
Department of Pathology, Hematopathology Section and Lymph Node Registry, Christian-Albrechts University, Kiel, Germany
Michael Baudis
Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland and Swiss Institute of Bioinformatics, University of Zurich, Zurich, Switzerland
Susanne Bens
Institute of Human Genetics, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Kiel, Germany
Laurence de Leval
Institute of Pathology, CHUV, University Hospital of Lausanne, Switzerland
Africa Garcia-Orad
Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country, UPV-EHU, Spain
Heike Horn
Department of Clinical Pathology, Robert-Bosch-Hospital and Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology Stuttgart, Germany
Jasmin Lisfeld
NHL-BFM Study Center, Department of Pediatric Hematology and Oncology, Justus-Liebig-University, Giessen, Germany
Shoji Pellissery
Institute of Human Genetics, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Kiel, Germany
Wolfram Klapper
Department of Pathology, Hematopathology Section and Lymph Node Registry, Christian-Albrechts University, Kiel, Germany
Ilske Oschlies
Department of Pathology, Hematopathology Section and Lymph Node Registry, Christian-Albrechts University, Kiel, Germany
Reiner Siebert
Institute of Human Genetics, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Kiel, Germany
Pediatric follicular lymphoma is a rare disease that differs genetically and clinically from its adult counterpart. With the exception of pediatric follicular lymphoma with IRF4-translocation, the genetic events associated with these lymphomas have not yet been defined. We applied array-comparative genomic hybridization and molecular inversion probe assay analyses to formalin-fixed paraffin-embedded tissues from 18 patients aged 18 years and under with IRF4 translocation negative follicular lymphoma. All evaluable cases lacked t(14;18). Only 6 of 16 evaluable cases displayed chromosomal imbalances with gains or amplifications of 6pter-p24.3 (including IRF4) and deletion and copy number neutral-loss of heterozygosity in 1p36 (including TNFRSF14) being most frequent. Sequencing of TNFRSF14 located in the minimal region of loss in 1p36.32 showed nine mutations in 7 cases from our series. Two subsets of pediatric follicular lymphoma were delineated according to the presence of molecular alterations, one with genomic aberrations associated with higher grade and/or diffuse large B-cell lymphoma component and more widespread disease, and another one lacking genetic alterations associated with more limited disease.
