TY - JOUR
T1 - PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice
AU - Weber, Julia
AU - de la Rosa, Jorge
AU - Grove, Carolyn S.
AU - Schick, Markus
AU - Rad, Lena
AU - Baranov, Olga
AU - Strong, Alexander
AU - Pfaus, Anja
AU - Friedrich, Mathias J.
AU - Engleitner, Thomas
AU - Lersch, Robert
AU - Öllinger, Rupert
AU - Grau, Michael
AU - Menendez, Irene Gonzalez
AU - Martella, Manuela
AU - Kohlhofer, Ursula
AU - Banerjee, Ruby
AU - Turchaninova, Maria A.
AU - Scherger, Anna
AU - Hoffman, Gary J.
AU - Hess, Julia
AU - Kuhn, Laura B.
AU - Ammon, Tim
AU - Kim, Johnny
AU - Schneider, Günter
AU - Unger, Kristian
AU - Zimber-Strobl, Ursula
AU - Heikenwälder, Mathias
AU - Schmidt-Supprian, Marc
AU - Yang, Fengtang
AU - Saur, Dieter
AU - Liu, Pentao
AU - Steiger, Katja
AU - Chudakov, Dmitriy M.
AU - Lenz, Georg
AU - Quintanilla-Martinez, Leticia
AU - Keller, Ulrich
AU - Vassiliou, George S.
AU - Cadiñanos, Juan
AU - Bradley, Allan
AU - Rad, Roland
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85063729846
U2 - 10.1038/s41467-019-09180-3
DO - 10.1038/s41467-019-09180-3
M3 - Article
C2 - 30926791
AN - SCOPUS:85063729846
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1415
ER -
