Role of ETS1 in the transcriptional network of diffuse large B cell lymphoma of the activated B cell-like type

Priebe, Valdemar; Sartori, Giulio; Napoli, Sara; Chung, Elaine Yee Lin; Cascione, Luciano; Kwee, Ivo; Arribas, Alberto Jesus; Mensah, Afua Adjeiwaa; Rinaldi, Andrea; Ponzoni, Maurilio; Zucca, Emanuele; Rossi, Davide; Efremov, Dimitar; Lenz, Georg; Thome, Margot; Bertoni, Francesco

doi:10.3390/cancers12071912

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Journal article

Role of ETS1 in the transcriptional network of diffuse large B cell lymphoma of the activated B cell-like type

Priebe, Valdemar Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Sartori, Giulio Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Napoli, Sara Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Chung, Elaine Yee Lin Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Cascione, Luciano Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland
Kwee, Ivo Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland - Istituto Dalle Molle di studi sull'intelligenza artificiale (IDSIA), Facoltà di scienze informatiche, Università della Svizzera italiana, Svizzera
Arribas, Alberto Jesus Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland
Mensah, Afua Adjeiwaa Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Rinaldi, Andrea Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Ponzoni, Maurilio San Raffaele Scientific Institute, Vita Salute University, Milan, Italy
Zucca, Emanuele Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland
Rossi, Davide Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland
Efremov, Dimitar Molecular Hematology, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy
Lenz, Georg Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Münster, Münster, Germany
Thome, Margot Department of Biochemistry, University of Lausanne, Epalinges, Switzerland
Bertoni, Francesco Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland

15.07.2020

Published in:

Cancers. - 2020, vol. 12, no. 7, p. 17 p

English Diffuse large B cell lymphoma (DLBCL) is a heterogenous disease that has been distinguished into at least two major molecular entities, the germinal center-like B cell (GCB) DLBCL and activated-like B cell (ABC) DLBCL, based on transcriptome expression profiling. A recurrent ch11q24.3 gain is observed in roughly a fourth of DLBCL cases resulting in the overexpression of two ETS transcription factor family members, ETS1 and FLI1. Here, we knocked down ETS1 expression by siRNA and analyzed expression changes integrating them with ChIP-seq data to identify genes directly regulated by ETS1. ETS1 silencing affected expression of genes involved in B cell signaling activation, B cell differentiation, cell cycle, and immune processes. Integration of RNA-Seq (RNA sequencing) data and ChIP-Seq (chromatin immunoprecipitation sequencing) identified 97 genes as bona fide, positively regulated direct targets of ETS1 in ABC-DLBCL. Among these was the Fc receptor for IgM, FCMR (also known as FAIM3 or Toso), which showed higher expression in ABC- than GCB-DLBCL clinical specimens. These findings show that ETS1 is contributing to the lymphomagenesis in a subset of DLBCL and identifies FCMR as a novel target of ETS1, predominantly expressed in ABC-DLBCL.

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