BACKGROUND: Prostate cancer (PC) is the commonest male visceral cancer, and second leading cause of cancer mortality in men in the Western world. METHODS: Using a forward-mutagenesis Sleeping Beauty (SB) transposon-based screen in a Probasin Cre-Recombinase (Pb-Cre) Pten-deficient mouse model of PC, we identified Arid1a loss as a driver in the development of metastatic disease. RESULTS: The insertion of transposon in the Arid1a gene resulted in a 60% reduction of Arid1a expression, and reduced tumour free survival (SB:Pten CONCLUSION: Our data revealed homozygous Arid1a loss is required to dramatically accelerate prostate tumourigenesis. Analysis of RNA and ChIP -Sequencing data suggests Arid1a loss enhanced the function of AP-1 subunit cFos. In clinical PC cohort, ARID1A and cFos levels stratified an aggressive subset of PC with a poor survival outcome with a median of only 30 months.