Molecular profiling of EBV associated diffuse large B-cell lymphoma

被引：41

作者：

Frontzek, Fabian ^{[1
]}

Staiger, Annette M. M. ^{[2
,3
,4
]}

Wullenkord, Ramona ^{[1
]}

Grau, Michael ^{[1
]}

Zapukhlyak, Myroslav ^{[1
]}

Kurz, Katrin S. S. ^{[2
]}

Horn, Heike ^{[2
,3
,4
]}

Erdmann, Tabea ^{[1
]}

Fend, Falko ^{[5
]}

Richter, Julia ^{[6
]}

Klapper, Wolfram ^{[6
]}

Lenz, Peter ^{[7
]}

Hailfinger, Stephan ^{[1
]}

Tasidou, Anna ^{[8
]}

Trautmann, Marcel ^{[9
]}

Hartmann, Wolfgang ^{[9
]}

Rosenwald, Andreas ^{[10
]}

Quintanilla-Martinez, Leticia ^{[5
]}

Ott, German ^{[2
,3
,4
]}

Anagnostopoulos, Ioannis ^{[10
]}

Lenz, Georg ^{[1
]}

机构：

[1] Univ Hosp Munster, Dept Hematol Oncol & Pneumol, Dept Med A, Munster, Germany

[2] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany

[3] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany

[4] Univ Tubingen, Tubingen, Germany

[5] Tubingen Eberhard Karls Univ, Reference Ctr Haematopathol Univ Hosp, Inst Pathol & Neuropathol, Tubingen, Germany

[6] Univ Kiel, Div Hematophathol, Kiel, Germany

[7] Univ Marburg, Dept Phys, Marburg, Germany

[8] Evangelismos Gen Hosp, Dept Hematopathol, Athens, Greece

[9] Univ Hosp Munster, Gerhard Domagk Inst Pathol, Div Translat Pathol, Munster, Germany

[10] Univ Wurzburg, Inst Pathol, Wurzburg, Germany

来源：

LEUKEMIA | 2023年 / 37卷 / 03期

关键词：

GENE-EXPRESSION; TUMOR-CELLS; MUTATIONS; CANCER; EBNA2; PREVALENCE; LANDSCAPE; SUBTYPES; GROWTH; NOTCH1;

D O I：

10.1038/s41375-022-01804-w

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Epstein-Barr virus (EBV) associated diffuse large B-cell lymphoma (DLBCL) represents a rare aggressive B-cell lymphoma subtype characterized by an adverse clinical outcome. EBV infection of lymphoma cells has been associated with different lymphoma subtypes while the precise role of EBV in lymphomagenesis and specific molecular characteristics of these lymphomas remain elusive. To further unravel the biology of EBV associated DLBCL, we present a comprehensive molecular analysis of overall 60 primary EBV positive (EBV+) DLBCLs using targeted sequencing of cancer candidate genes (CCGs) and genome-wide determination of recurrent somatic copy number alterations (SCNAs) in 46 cases, respectively. Applying the LymphGen classifier 2.0, we found that less than 20% of primary EBV + DLBCLs correspond to one of the established molecular DLBCL subtypes underscoring the unique biology of this entity. We have identified recurrent mutations activating the oncogenic JAK-STAT and NOTCH pathways as well as frequent amplifications of 9p24.1 contributing to immune escape by PD-L1 overexpression. Our findings enable further functional preclinical and clinical studies exploring the therapeutic potential of targeting these aberrations in patients with EBV + DLBCL to improve outcome.

引用

页码：670 / 679

页数：10

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