Deregulation of ETS1 and FLI1 contributes to the pathogenesis of diffuse large B-cell lymphoma.
Diffuse large B-cell lymphoma (DLBCL) is the most common form of human lymphoma. DLBCL is a heterogeneous disease characterized by different genetic lesions. We herein report the functional characterization of a recurrent gain mapping on chromosome 11q24.3, found in 23% of 166 DLBCL cases analyzed. The transcription factors ETS1 and FLI1, located within the 11q24.3 region, had significantly higher expression in clinical samples carrying the gain. Functional studies on cell lines showed that ETS1 and FLI1 cooperate in sustaining DLBCL proliferation and viability and regulate genes involved in germinal center differentiation. Taken together, these data identify the 11q24.3 gain as a recurrent lesion in DLBCL leading to ETS1 and FLI1 deregulated expression, which can contribute to the pathogenesis of this disease.
Lymphoma and Genomics Research Program, Institute of Oncology Research, Bellinzona, Switzerland;
Paola
P
Bonetti
Monica
M
Testoni
Marta
M
Scandurra
Maurilio
M
Ponzoni
Roberto
R
Piva
Afua A
AA
Mensah
Andrea
A
Rinaldi
Ivo
I
Kwee
Maria Grazia
MG
Tibiletti
Javeed
J
Iqbal
Timothy C
TC
Greiner
Wing-Chung
WC
Chan
Gianluca
G
Gaidano
Miguel A
MA
Piris
Franco
F
Cavalli
Emanuele
E
Zucca
Giorgio
G
Inghirami
Francesco
F
Bertoni
D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D018274:Electroporation; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D050784:Proto-Oncogene Protein c-ets-1 / Q000096:biosynthesis / Q000235:genetics*; D051789:Proto-Oncogene Protein c-fli-1 / Q000096:biosynthesis / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome; D014162:Transfection
C494041:ETS1 protein, human; C078433:FLI1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D051789:Proto-Oncogene Protein c-fli-1