| Title: |
PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice. |
| Authors: |
Weber, Julia; de la Rosa, Jorge; Grove, Carolyn S; Schick, Markus; Rad, Lena; Baranov, Olga; Strong, Alexander; Pfaus, Anja; Friedrich, Mathias J; Engleitner, Thomas; Lersch, Robert; Öllinger, Rupert; Grau, Michael; Menendez, Irene Gonzalez; Martella, Manuela; Kohlhofer, Ursula; Banerjee, Ruby; Turchaninova, Maria A; Scherger, Anna; Hoffman, Gary J; Hess, Julia; Kuhn, Laura B; Ammon, Tim; Kim, Johnny; Schneider, Günter; Unger, Kristian; Zimber-Strobl, Ursula; Heikenwälder, Mathias; Schmidt-Supprian, Marc; Yang, Fengtang; Saur, Dieter; Liu, Pentao; Steiger, Katja; Chudakov, Dmitriy M; Lenz, Georg; Quintanilla-Martinez, Leticia; Keller, Ulrich; Vassiliou, George S; Cadiñanos, Juan; Bradley, Allan; Rad, Roland |
| Publisher Information: |
Springer Nature; //doi.org/10.1038/s41467-019-09180-3 |
| Publication Year: |
2019 |
| Collection: |
Apollo - University of Cambridge Repository |
| Subject Terms: |
Animals; CRISPR-Cas Systems; Clone Cells; DNA Transposable Elements; Gene Dosage; Gene Expression Regulation; Neoplastic; Genes; Neoplasm; Tumor Suppressor; Genetic Association Studies; Genetic Testing; Humans; Loss of Heterozygosity; Lymphoma; B-Cell; Mice; Inbred C57BL; Transgenic; Receptors; Antigen; Reproducibility of Results |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
Electronic; application/pdf |
| Language: |
English |
| Relation: |
https://www.repository.cam.ac.uk/handle/1810/292485 |
| DOI: |
10.17863/CAM.39645 |
| Availability: |
https://www.repository.cam.ac.uk/handle/1810/292485; https://doi.org/10.17863/CAM.39645 |
| Rights: |
Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.8C6166D |
| Database: |
BASE |