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PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice
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Zeitschriftentitel: | Nature Communications |
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Personen und Körperschaften: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
In: | Nature Communications, 10, 2019, 1 |
Format: | E-Article |
Sprache: | Englisch |
veröffentlicht: |
Springer Science and Business Media LLC
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Schlagwörter: |
Zusammenfassung: | <jats:title>Abstract</jats:title><jats:p>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 <jats:italic>PiggyBac</jats:italic> 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 <jats:italic>in vivo</jats:italic> platform for BCL functional genomics, and validate discovered genes, such as <jats:italic>Rfx7</jats:italic>, a transcription factor, and <jats:italic>Phip</jats:italic>, 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.</jats:p> |
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ISSN: |
2041-1723
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DOI: | 10.1038/s41467-019-09180-3 |