Role of ETS1 in the Transcriptional Network of Diffuse Large B Cell Lymphoma of the Activated B Cell-Like Type
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 observ...
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doaj-0ca635d1c9f5418395e644c03401ced72020-11-25T03:10:16ZengMDPI AGCancers2072-66942020-07-01121912191210.3390/cancers12071912Role of ETS1 in the Transcriptional Network of Diffuse Large B Cell Lymphoma of the Activated B Cell-Like TypeValdemar Priebe0Giulio Sartori1Sara Napoli2Elaine Yee Lin Chung3Luciano Cascione4Ivo Kwee5Alberto Jesus Arribas6Afua Adjeiwaa Mensah7Andrea Rinaldi8Maurilio Ponzoni9Emanuele Zucca10Davide Rossi11Dimitar Efremov12Georg Lenz13Margot Thome14Francesco Bertoni15Institute of Oncology Research, Faculty of Biomedical Sciences, USI, 6500 Bellinzona, SwitzerlandInstitute of Oncology Research, Faculty of Biomedical Sciences, USI, 6500 Bellinzona, SwitzerlandInstitute of Oncology Research, Faculty of Biomedical Sciences, USI, 6500 Bellinzona, SwitzerlandInstitute of Oncology Research, Faculty of Biomedical Sciences, USI, 6500 Bellinzona, SwitzerlandInstitute of Oncology Research, Faculty of Biomedical Sciences, USI, 6500 Bellinzona, SwitzerlandInstitute of Oncology Research, Faculty of Biomedical Sciences, USI, 6500 Bellinzona, SwitzerlandInstitute of Oncology Research, Faculty of Biomedical Sciences, USI, 6500 Bellinzona, SwitzerlandInstitute of Oncology Research, Faculty of Biomedical Sciences, USI, 6500 Bellinzona, SwitzerlandInstitute of Oncology Research, Faculty of Biomedical Sciences, USI, 6500 Bellinzona, SwitzerlandSan Raffaele Scientific Institute, Vita Salute University, 20132 Milan, ItalyInstitute of Oncology Research, Faculty of Biomedical Sciences, USI, 6500 Bellinzona, SwitzerlandInstitute of Oncology Research, Faculty of Biomedical Sciences, USI, 6500 Bellinzona, SwitzerlandMolecular Hematology, International Centre for Genetic Engineering and Biotechnology, 34149 Trieste, ItalyDepartment of Medicine A, Hematology, Oncology and Pneumology, University Hospital Münster, 48149 Münster, GermanyDepartment of Biochemistry, University of Lausanne, 1066 Epalinges, SwitzerlandInstitute of Oncology Research, Faculty of Biomedical Sciences, USI, 6500 Bellinzona, SwitzerlandDiffuse 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.https://www.mdpi.com/2072-6694/12/7/1912diffuse large B cell lymphomaETS1BCL6PRDM1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Valdemar Priebe Giulio Sartori Sara Napoli Elaine Yee Lin Chung Luciano Cascione Ivo Kwee Alberto Jesus Arribas Afua Adjeiwaa Mensah Andrea Rinaldi Maurilio Ponzoni Emanuele Zucca Davide Rossi Dimitar Efremov Georg Lenz Margot Thome Francesco Bertoni |
spellingShingle |
Valdemar Priebe Giulio Sartori Sara Napoli Elaine Yee Lin Chung Luciano Cascione Ivo Kwee Alberto Jesus Arribas Afua Adjeiwaa Mensah Andrea Rinaldi Maurilio Ponzoni Emanuele Zucca Davide Rossi Dimitar Efremov Georg Lenz Margot Thome Francesco Bertoni Role of ETS1 in the Transcriptional Network of Diffuse Large B Cell Lymphoma of the Activated B Cell-Like Type Cancers diffuse large B cell lymphoma ETS1 BCL6 PRDM1 |
author_facet |
Valdemar Priebe Giulio Sartori Sara Napoli Elaine Yee Lin Chung Luciano Cascione Ivo Kwee Alberto Jesus Arribas Afua Adjeiwaa Mensah Andrea Rinaldi Maurilio Ponzoni Emanuele Zucca Davide Rossi Dimitar Efremov Georg Lenz Margot Thome Francesco Bertoni |
author_sort |
Valdemar Priebe |
title |
Role of ETS1 in the Transcriptional Network of Diffuse Large B Cell Lymphoma of the Activated B Cell-Like Type |
title_short |
Role of ETS1 in the Transcriptional Network of Diffuse Large B Cell Lymphoma of the Activated B Cell-Like Type |
title_full |
Role of ETS1 in the Transcriptional Network of Diffuse Large B Cell Lymphoma of the Activated B Cell-Like Type |
title_fullStr |
Role of ETS1 in the Transcriptional Network of Diffuse Large B Cell Lymphoma of the Activated B Cell-Like Type |
title_full_unstemmed |
Role of ETS1 in the Transcriptional Network of Diffuse Large B Cell Lymphoma of the Activated B Cell-Like Type |
title_sort |
role of ets1 in the transcriptional network of diffuse large b cell lymphoma of the activated b cell-like type |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2020-07-01 |
description |
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. |
topic |
diffuse large B cell lymphoma ETS1 BCL6 PRDM1 |
url |
https://www.mdpi.com/2072-6694/12/7/1912 |
work_keys_str_mv |
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