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

Nat. Commun. 10:1415 (2019)
Publishers Version Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
as soon as is submitted to ZB.
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
Reviewing status