Role of BAP1 in pancreatic cancer (ChIP-seq Mus musculus)

We found that BAP1 (BRCA1 Associated Protein-1) shows loss of heterozygosity in over 25% of pancreatic cancer patients and functions as tumor suppressor. Conditional deletion of Bap1 in murine pancreas led to genomic instability, accumulation of DNA damage, and an inflammatory response that evolved to pancreatitis with full penetrance. Concomitant expression of oncogenic KrasG12D led to malignant transformation and development of invasive and metastatic pancreatic cancer. At the molecular level, BAP1 maintains the integrity of the exocrine pancreas by regulating genomic stability and its loss confers sensitivity to radio- and platinum-based therapies. Murine cell lines were estabished from Bap1 null pancreata expressing KrasG12D and analyzed by ChIP-seq for H3K4me1, H3K4me3, H3K27me3, H3K27ac, H2AK119ub, and H2BK120ub.