| Literature DB >> 25485836 |
Roland Rad1, Lena Rad2, Wei Wang2, Alexander Strong2, Hannes Ponstingl2, Iraad F Bronner2, Matthew Mayho2, Katja Steiger3, Julia Weber4, Maren Hieber5, Christian Veltkamp5, Stefan Eser5, Ulf Geumann4, Rupert Öllinger5, Magdalena Zukowska5, Maxim Barenboim4, Roman Maresch4, Juan Cadiñanos6, Mathias Friedrich2, Ignacio Varela7, Fernando Constantino-Casas8, Aaron Sarver9, Jelle Ten Hoeve10, Haydn Prosser2, Barbara Seidler5, Judith Bauer11, Mathias Heikenwälder11, Emmanouil Metzakopian2, Anne Krug5, Ursula Ehmer5, Günter Schneider5, Thomas Knösel12, Petra Rümmele13, Daniela Aust14, Robert Grützmann15, Christian Pilarsky15, Zemin Ning2, Lodewyk Wessels10, Roland M Schmid5, Michael A Quail2, George Vassiliou2, Irene Esposito16, Pentao Liu2, Dieter Saur4, Allan Bradley2.
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.Entities:
Mesh：
Substances：
Year: 2014 PMID： 25485836 DOI： 10.1038/ng.3164
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330