%0 Journal Article %1 Salaverria.2011 %A Salaverria, Itziar %A Philipp, Claudia %A Oschlies, Ilske %A Kohler, Christian W. %A Kreuz, Markus %A Szczepanowski, Monika %A Burkhardt, Birgit %A Trautmann, Heiko %A Gesk, Stefan %A Andrusiewicz, Miroslaw %A Berger, Hilmar %A Fey, Miriam %A Harder, Lana %A Hasenclever, Dirk %A Hummel, Michael %A Loeffler, Markus %A Mahn, Friederike %A Martin-Guerrero, Idoia %A Pellissery, Shoji %A Pott, Christiane %A Pfreundschuh, Michael %A Reiter, Alfred %A Richter, Julia %A Rosolowski, Maciej %A Schwaenen, Carsten %A Stein, Harald %A Trümper, Lorenz %A Wessendorf, Swen %A Spang, Rainer %A Küppers, Ralf %A Klapper, Wolfram %A Siebert, Reiner %D 2011 %J Blood %K Adolescent Adult Age_of_Onset Aged Base_Sequence Child Child,_Preschool Chromosomes,_Human,_Pair_14 Chromosomes,_Human,_Pair_6 Female Genes,_Immunoglobulin_Heavy_Chain/genetics/immunology Germinal_Center/pathology Humans Interferon_Regulatory_Factors/genetics/immunology Lymphoma,_B-Cell/genetics/immunology/pathology Male Middle_Aged Molecular_Sequence_Data Oncogene_Proteins,_Fusion/genetics Prognosis Translocation,_Genetic Young_Adult %N 1 %P 139–147 %T Translocations activating IRF4 identify a subtype of germinal center-derived B-cell lymphoma affecting predominantly children and young adults %V 118 %X 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.

@article{Salaverria.2011, 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.}, added-at = {2014-10-14T15:28:09.000+0200}, author = {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 Trümper, Lorenz and Wessendorf, Swen and Spang, Rainer and Küppers, Ralf and Klapper, Wolfram and Siebert, Reiner}, biburl = {https://www.bibsonomy.org/bibtex/2ab9ee18cda99bf545b740e0657975a78/drtester}, interhash = {2814ffc4d4139aa25eea060dc6294027}, intrahash = {ab9ee18cda99bf545b740e0657975a78}, journal = {Blood}, keywords = {Adolescent Adult Age_of_Onset Aged Base_Sequence Child Child,_Preschool Chromosomes,_Human,_Pair_14 Chromosomes,_Human,_Pair_6 Female Genes,_Immunoglobulin_Heavy_Chain/genetics/immunology Germinal_Center/pathology Humans Interferon_Regulatory_Factors/genetics/immunology Lymphoma,_B-Cell/genetics/immunology/pathology Male Middle_Aged Molecular_Sequence_Data Oncogene_Proteins,_Fusion/genetics Prognosis Translocation,_Genetic Young_Adult}, number = 1, pages = {139–147}, timestamp = {2014-10-14T15:28:09.000+0200}, title = {Translocations activating IRF4 identify a subtype of germinal center-derived B-cell lymphoma affecting predominantly children and young adults}, volume = 118, year = 2011 }