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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
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    15.07.2020
Published in:
  • Cancers. - 2020, vol. 12, no. 7, p. 17 p
Diffuse large B cell lymphoma
ETS1
BCL6
PRDM1
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.
Language
  • English
Classification
Pathology, clinical medicine
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https://n2t.net/ark:/12658/srd1319192
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