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High resolution copy number analysis of IRF4 translocation‐positive diffuse large B‐cell and follicular lymphomas
Authors:Idoia Martin‐Guerrero  Birgit Burkhardt  Markus Kreuz  Thorsten Zenz  Ilske Oschlies  Norbert Arnold  Michael Baudis  Susanne Bens  Africa García‐Orad  Jasmin Lisfeld  Carsten Schwaenen  Monika Szczepanowski  Swen Wessendorf  Michael Pfreundschuh  Lorenz Trümper  Wolfram Klapper  Reiner Siebert
Institution:1. Institute of Human Genetics, University Hospital Schleswig‐Holstein Campus Kiel/Christian‐Albrechts University, Kiel, Germany;2. Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country, Leioa, Bizkaia, SpainItziar Salaverria and Idoia Martin‐Guerrero contributed equally to this work.;3. NHL‐BFM Study Center, Department of Pediatric Hematology and Oncology, Justus‐Liebig‐University, Giessen, Germany;4. Pediatric Hematology and Oncology, University Hospital Münster, Münster, Germany;5. Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany;6. Department of Translational Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany;7. Department of Internal Medicine V, University Hospital Heidelberg, Germany;8. Department of Pathology, Hematopathology Section and Lymph Node Registry, Christian‐Albrechts University, Kiel, Germany;9. Department of Gynecology and Obstetrics, University Hospital Schleswig‐Holstein Campus Kiel/Christian‐Albrechts University, Kiel, Germany;10. Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland;11. Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country, Leioa, Bizkaia, Spain;12. Internal Medicine III, University Hospital of Ulm, Ulm, Germany;13. Department of Internal Medicine I, University of Saarland, Homburg, Germany;14. Department of Hematology and Oncology, Georg‐August University of G?ttingen, G?ttingen, Germany
Abstract:Translocations affecting chromosome subband 6p25.3 containing the IRF4 gene have been recently described as characteristic alterations in a molecularly distinct subset of germinal center B‐cell‐derived lymphomas. Secondary changes have yet only been described in few of these lymphomas. Here, we performed array‐comparative genomic hybridization and molecular inversion probe microarray analyses on DNA from 12 formalin‐fixed paraffin‐embedded and two fresh‐frozen IRF4 translocation‐positive lymphomas, which together with the previously published data on nine cases allowed the extension of copy number analyses to a total of 23 of these lymphomas. All except one case carried chromosomal imbalances, most frequently gains in Xq28, 11q22.3‐qter, and 7q32.1‐qter and losses in 6q13‐16.1, 15q14‐22.31, and 17p. No recurrent copy‐neutral losses of heterozygosity were observed. TP53 point mutations were detected in three of six cases with loss of 17p. Overall this study unravels a recurrent pattern of secondary genetic alterations in IRF4 translocation‐positive lymphomas. © 2012 Wiley Periodicals, Inc.
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