PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice.
- Weber, J.
- de la Rosa, J.
- Grove, C.S.
- Schick, M.
- Rad, L.
- Baranov, O.
- Strong, A.
- Pfaus, A.
- Friedrich, M.J.
- Engleitner, T.
- Lersch, R.
- Öllinger, R.
- Grau, M.
- Menendez, I.G.
- Martella, M.
- Kohlhofer, U.
- Banerjee, R.
- Turchaninova, M.A.
- Scherger, A.
- Hoffman, G.J.
- Hess-Rieger, J.
- Kuhn, L.
- Ammon, T.
- Kim, J.
- Schneider, G.
- Unger, K.
- Zimber-Strobl, U.
- Heikenwälder, M.
- Schmidt-Supprian, M.
- Yang, F.
- Saur, D.
- Liu, P.
- Steiger, K.
- Chudakov, D.M.
- Lenz, G.
- Quintanilla-Martinez, L.
- Keller, U.
- Vassiliou, G.S.
- Cadiñanos, J.
- Bradley, A.
- Rad, R.
DOIAbstract
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...
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