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

被引：206

作者：

Salaverria, Itziar ^{[1
]}

Philipp, Claudia ^{[2
]}

Oschlies, Ilske ^{[3
]}

Kohler, Christian W. ^{[4
]}

Kreuz, Markus ^{[5
]}

Szczepanowski, Monika ^{[3
]}

Burkhardt, Birgit ^{[6
]}

Trautmann, Heiko ^{[7
]}

Gesk, Stefan ^{[1
]}

Andrusiewicz, Miroslaw ^{[1
,8
]}

Berger, Hilmar ^{[5
]}

Fey, Miriam ^{[1
]}

Harder, Lana ^{[1
]}

Hasenclever, Dirk ^{[5
]}

Hummel, Michael ^{[9
]}

Loeffler, Markus ^{[5
]}

Mahn, Friederike ^{[1
]}

Martin-Guerrero, Idoia ^{[1
]}

Pellissery, Shoji ^{[1
]}

Pott, Christiane ^{[7
]}

Pfreundschuh, Michael ^{[10
]}

Reiter, Alfred ^{[6
]}

Richter, Julia ^{[1
]}

Rosolowski, Maciej ^{[5
]}

Schwaenen, Carsten ^{[11
]}

Stein, Harald ^{[9
]}

Truemper, Lorenz ^{[12
]}

Wessendorf, Swen ^{[11
]}

Spang, Rainer

Kueppers, Ralf ^{[2
]}

Klapper, Wolfram ^{[3
]}

Siebert, Reiner ^{[1
]}

机构：

[1] Univ Kiel, Inst Human Genet, Univ Hosp Schleswig Holstein, D-24105 Kiel, Germany

[2] Univ Duisburg Essen, Sch Med, Inst Cell Biol Canc Res, Essen, Germany

[3] Univ Kiel, Univ Hosp Schleswig Holstein, Hematopathol Sect & Lymph Node, Dept Pathol, D-24105 Kiel, Germany

[4] Univ Regensburg, Inst Funct Genom, Regensburg, Germany

[5] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany

[6] Univ Giessen, Dept Pediat Hematol & Oncol, Giessen, Germany

[7] Univ Kiel, Dept Med 2, Univ Hosp Schleswig Holstein, D-24105 Kiel, Germany

[8] Univ Med Sci, Dept Cell Biol, Poznan, Poland

[9] Charite Univ Med Berlin, Inst Pathol, Berlin, Germany

[10] Univ Saarland, Dept Internal Med 1, D-6650 Homburg, Germany

[11] Univ Hosp Ulm, Ulm, Germany

[12] Univ Gottingen, Dept Hematol & Oncol, Gottingen, Germany

来源：

BLOOD | 2011年 / 118卷 / 01期

关键词：

NON-HODGKINS-LYMPHOMAS; FOLLICULAR LYMPHOMA; MULTIPLE-MYELOMA; GENE-EXPRESSION; CLINICOPATHOLOGICAL ANALYSIS; BURKITTS-LYMPHOMA; SURVIVAL; TRIALS; CHEMOTHERAPY; MECHANISMS;

D O I：

10.1182/blood-2011-01-330795

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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)

引用

页码：139 / 147

页数：9

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