Rad, Roland and Rad, Lena and Wang, Wei and Strong, Alexander and Ponstingl, Hannes and Bronner, Iraad F. and Mayho, Matthew and Steiger, Katja and Weber, Julia and Hieber, Maren and Veltkamp, Christian and Eser, Stefan and Geumann, Ulf and Oellinger, Rupert and Zukowska, Magdalena and Barenboim, Maxim and Maresch, Roman and Cadinanos, Juan and Friedrich, Mathias and Varela, Ignacio and Constantino-Casas, Fernando and Sarver, Aaron and ten Hoeve, Jelle and Prosser, Haydn and Seidler, Barbara and Bauer, Judith and Heikenwaelder, Mathias and Metzakopian, Emmanouil and Krug, Anne and Ehmer, Ursula and Schneider, Guenter and Knoesel, Thomas and Ruemmele, Petra and Aust, Daniela and Gruetzmann, Robert and Pilarsky, Christian and Ning, Zemin and Wessels, Lodewyk and Schmid, Roland M. and Quail, Michael A. and Vassiliou, George and Esposito, Irene and Liu, Pentao and Saur, Dieter and Bradley, Allan (2015) A conditional piggyBac transposition system for genetic screening in mice identifies oncogenic networks in pancreatic cancer. NATURE GENETICS, 47 (1). 47-+. ISSN 1061-4036, 1546-1718
Full text not available from this repository. (Request a copy)Abstract
Here we describe a conditional piggyBac transposition system in mice and report the discovery of large sets of new cancer genes through a pancreatic insertional mutagenesis screen. We identify Foxp1 as an oncogenic transcription factor that drives pancreatic cancer invasion and spread in a mouse model and correlates with lymph node metastasis in human patients with pancreatic cancer. The propensity of piggyBac for open chromatin also enabled genome-wide screening for cancer-relevant noncoding DNA, which pinpointed a Cdkn2a cis-regulatory region. Histologically, we observed different tumor subentities and discovered associated genetic events, including Fign insertions in hepatoid pancreatic cancer. Our studies demonstrate the power of genetic screening to discover cancer drivers that are difficult to identify by other approaches to cancer genome analysis, such as downstream targets of commonly mutated human cancer genes. These piggyBac resources are universally applicable in any tissue context and provide unique experimental access to the genetic complexity of cancer.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SLEEPING-BEAUTY; CHROMOSOMAL TRANSPOSITION; SOMATIC MUTAGENESIS; EXPRESSION; TOOL; LANDSCAPE; DISCOVERY; PROTEINS; FIDGETIN; PATHWAYS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Aug 2019 12:51 |
| Last Modified: | 02 Aug 2019 12:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/6363 |
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