Figure 3. Pbrm1 is frequently mutated in a mouse model of pancreatic cancer.

To identify genes that co-operate with K-Ras in the formation of pancreatic cancer a conditional allele of K-Ras^G12D and Pdx1-Cre were combined with a conditional Sleeping Beauty transposase driver and the T2Onc^tg transposon donor allele²⁹. Expression of Cre results in expression of K-Ras^G12D and transposon mobilization within the epithelial compartment of the pancreas. Isolation of the transposon insertion sites from a panel of 153 pancreatic cancers and pre-neoplastic lesions generated from this model revealed a common insertion site in Pbrm1 suggesting that loss of Pbrm1 co-operates with K-Ras^G12D in pancreatic cancer development. Statistical analysis was performed as previously described³⁰. Transposon insertions in the forward strand of Pbrm1 are shown in green. Insertions in the reverse orientation are shown in red. A chromatogram from sequencing of RT-PCR products from one tumour is shown demonstrating splicing of exon 24 of Pbrm1 into the inserted transposon, thus truncating the transcript.