Translocations activating IRF4 identify a subtype of germinal center-derived B-cell lymphoma affecting predominantly children and young adults

Salaverria, Itziar and Philipp, Claudia and Oschlies, Ilske and Kohler, Christian W. and Kreuz, Markus and Szczepanowski, Monika and Burkhardt, Birgit and Trautmann, Heiko and Gesk, Stefan and Andrusiewicz, Miroslaw and Berger, Hilmar and Fey, Miriam and Harder, Lana and Hasenclever, Dirk and Hummel, Michael and Loeffler, Markus and Mahn, Friederike and Martin-Guerrero, Idoia and Pellissery, Shoji and Pott, Christiane and Pfreundschuh, Michael and Reiter, Alfred and Richter, Julia and Rosolowski, Maciej and Schwaenen, Carsten and Stein, Harald and Truemper, Lorenz and Wessendorf, Swen and Spang, Rainer and Kueppers, Ralf and Klapper, Wolfram and Siebert, Reiner (2011) Translocations activating IRF4 identify a subtype of germinal center-derived B-cell lymphoma affecting predominantly children and young adults. BLOOD, 118 (1). pp. 139-147. ISSN 0006-4971, 1528-0020

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Abstract

The prognosis of germinal center-derived B-cell (GCB) lymphomas, including follicular lymphoma and diffuse large-B-cell lymphoma (DLBCL), strongly depends on age. Children have a more favorable outcome than adults. It is not known whether this is because of differences in host characteristics, treatment protocols, or tumor biology, including the presence of chromosomal alterations. By screening for novel IGH translocation partners in pediatric and adult lymphomas, we identified chromosomal translocations juxtaposing the IRF4 oncogene next to one of the immunoglobulin (IG) loci as a novel recurrent aberration in mature B-cell lymphoma. FISH revealed 20 of 427 lymphomas to carry an IG/IRF4-fusion. Those were predominantly GCB-type DLBCL or follicular lymphoma grade 3, shared strong expression of IRF4/MUM1 and BCL6, and lacked PRDM1/BLIMP1 expression and t(14;18)/BCL2 breaks. BCL6 aberrations were common. The gene expression profile of IG/IRF4-positive lymphomas differed from other subtypes of DLBCL. A classifier for IG/IRF4 positivity containing 27 genes allowed accurate prediction. IG/IRF4 positivity was associated with young age and a favorable outcome. Our results suggest IRF4 translocations to be primary alterations in a molecularly defined subset of GCB-derived lymphomas. The probability for this subtype of lymphoma significantly decreases with age, suggesting that diversity in tumor biology might contribute to the age-dependent differences in prognosis of lymphoma. (Blood. 2011;118(1):139-147)

Item Type: Article
Uncontrolled Keywords: NON-HODGKINS-LYMPHOMAS; FOLLICULAR LYMPHOMA; MULTIPLE-MYELOMA; GENE-EXPRESSION; CLINICOPATHOLOGICAL ANALYSIS; BURKITTS-LYMPHOMA; SURVIVAL; TRIALS; CHEMOTHERAPY; MECHANISMS;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 08 Jun 2020 05:20
Last Modified: 08 Jun 2020 05:20
URI: https://pred.uni-regensburg.de/id/eprint/20546

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