WEBER, J., J. DELA ROSA, C.S. GROVE, M. SCHICK, L. RAD, O. BARANOVT, A. STRONG, A. PFAUS, M.J. FRIEDRICH, T. ENGLEITNER, R. LERSCH, R. OLLINGER, M. GRAU, I.G. MENENDEZ, M. MARTELLA, U. KOHLHOFER, R. BANERJEE, M.A. TURCHANINOVA, A. SCHERGER, G.J. HOFFMAN, J. HESS, L.B. KUH, T. AMMON, J. KIM, G. SCHNEIDER, K. UNGER, U. ZIMBER-STROBL, M. HEIKENWALDER, M. SCHMIDT-SUPPRIAN, F.T. YANG, D. SAUR, P.T. LIU, K. STEIGER, Dmitriy CHUDAKOV, G. LENZ, L. QUINTANILLA-MARTINEZ, U. KELLER, G.S. VASSILIOU, J. CADINANOS, A. BRADLEY and R. RAD. PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice. Nature Communications. London: Nature Publishing Group, 2019, vol. 10, MAR, p. 1-16. ISSN 2041-1723. Available from: https://dx.doi.org/10.1038/s41467-019-09180-3.
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Basic information
Original name PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice
Authors WEBER, J., J. DELA ROSA, C.S. GROVE, M. SCHICK, L. RAD, O. BARANOVT, A. STRONG, A. PFAUS, M.J. FRIEDRICH, T. ENGLEITNER, R. LERSCH, R. OLLINGER, M. GRAU, I.G. MENENDEZ, M. MARTELLA, U. KOHLHOFER, R. BANERJEE, M.A. TURCHANINOVA, A. SCHERGER, G.J. HOFFMAN, J. HESS, L.B. KUH, T. AMMON, J. KIM, G. SCHNEIDER, K. UNGER, U. ZIMBER-STROBL, M. HEIKENWALDER, M. SCHMIDT-SUPPRIAN, F.T. YANG, D. SAUR, P.T. LIU, K. STEIGER, Dmitriy CHUDAKOV (643 Russian Federation, guarantor, belonging to the institution), G. LENZ, L. QUINTANILLA-MARTINEZ, U. KELLER, G.S. VASSILIOU, J. CADINANOS, A. BRADLEY and R. RAD.
Edition Nature Communications, London, Nature Publishing Group, 2019, 2041-1723.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10608 Biochemistry and molecular biology
Country of publisher United Kingdom of Great Britain and Northern Ireland
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 12.121
RIV identification code RIV/00216224:14740/19:00113244
Organization unit Central European Institute of Technology
Doi http://dx.doi.org/10.1038/s41467-019-09180-3
UT WoS 000462721900014
Keywords in English CANCER GENE DISCOVERY; SLEEPING-BEAUTY; CHROMOSOMAL TRANSPOSITION; INSERTIONAL MUTAGENESIS; THERAPEUTIC TARGETS; CODING GENOME; MOUSE MODEL; PATHOGENESIS; ACTIVATION; MUTATION
Tags rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Pavla Foltynová, Ph.D., učo 106624. Changed: 31/3/2020 21:48.
Abstract
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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