A conditional piggyBac transposition system for genetic screening in mice identifies oncogenic networks in pancreatic cancer

Nat Genet. 2015 Jan;47(1):47-56. doi: 10.1038/ng.3164. Epub 2014 Dec 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Transformation, Neoplastic / genetics*
  • DNA Transposable Elements / genetics*
  • Forkhead Transcription Factors / analysis
  • Forkhead Transcription Factors / antagonists & inhibitors
  • Forkhead Transcription Factors / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Knock-In Techniques
  • Gene Regulatory Networks*
  • Genes, Synthetic
  • Genes, p16
  • Humans
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Moths / genetics
  • Mutagenesis, Insertional*
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Pancreatic Neoplasms / chemistry
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Proton-Translocating ATPases / genetics
  • RNA, Small Interfering / pharmacology
  • Repressor Proteins / analysis
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / genetics
  • Transgenes
  • Transposases / genetics
  • Transposases / physiology


  • DNA Transposable Elements
  • FOXP1 protein, human
  • Forkhead Transcription Factors
  • Foxp1 protein, mouse
  • Foxp2 protein, mouse
  • Neoplasm Proteins
  • RNA, Small Interfering
  • Repressor Proteins
  • Transposases
  • Proton-Translocating ATPases

Associated data

  • BioProject/PRJNA266573
  • SRA/SRP049610