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Weber, J.* ; de la Rosa, J.* ; Grove, C.S.* ; Schick, M.* ; Rad, L.* ; Baranov, O.* ; Strong, A.* ; Pfaus, A.* ; Friedrich, M.J.* ; Engleitner, T.* ; Lersch, R.* ; Öllinger, R.* ; Grau, M.* ; Menendez, I.G.* ; Martella, M.* ; Kohlhofer, U.* ; Banerjee, R.* ; Turchaninova, M.A.* ; Scherger, A.* ; Hoffman, G.J.* ; Hess J. ; Kuhn, L. ; Ammon, T.* ; Kim, J.* ; Schneider, G.* ; Unger, K. ; Zimber-Strobl, U. ; Heikenwälder, M.* ; Schmidt-Supprian, M.* ; Yang, F.* ; Saur, D.* ; Liu, P.* ; Steiger, K.* ; Chudakov, D.M.* ; Lenz, G.* ; Quintanilla-Martinez, L.* ; Keller, U.* ; Vassiliou, G.S.* ; Cadiñanos, J.* ; Bradley, A.* ; Rad, R.*

PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice.

Nat. Commun. 10:1415 (2019)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
B-cell lymphoma (BCL) is the most common hematologic malignancy. While sequencing studies gave insights into BCL genetics, identification of non-mutated cancer genes remains challenging. Here, we describe PiggyBac transposon tools and mouse models for recessive screening and show their application to study clonal B-cell lymphomagenesis. In a genome-wide screen, we discover BCL genes related to diverse molecular processes, including signaling, transcriptional regulation, chromatin regulation, or RNA metabolism. Cross-species analyses show the efficiency of the screen to pinpoint human cancer drivers altered by non-genetic mechanisms, including clinically relevant genes dysregulated epigenetically, transcriptionally, or post-transcriptionally in human BCL. We also describe a CRISPR/Cas9-based in vivo platform for BCL functional genomics, and validate discovered genes, such as Rfx7, a transcription factor, and Phip, a chromatin regulator, which suppress lymphomagenesis in mice. Our study gives comprehensive insights into the molecular landscapes of BCL and underlines the power of genome-scale screening to inform biology.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Cancer Gene Discovery; Sleeping-beauty; Chromosomal Transposition; Insertional Mutagenesis; Therapeutic Targets; Coding Genome; Mouse Model; Pathogenesis; Activation; Mutation
Language
Publication Year 2019
HGF-reported in Year 2019
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 10, Issue: 1, Pages: , Article Number: 1415 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Translational Metabolic Oncology (IDC-TMO)
Research Unit Gene Vector (AGV)
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Radiation Sciences
Immune Response and Infection
PSP Element(s) G-501000-001
G-501500-003
DOI 10.1038/s41467-019-09180-3
WOS ID WOS:000462721900014
Scopus ID 85063729846
PubMed ID 30926791
Erfassungsdatum 2019-04-04
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