KDM6A mutation in mouse model of bladder cancer

The Cancer Genome Atlas (TCGA) performed comprehensive molecular characterization of over 400 muscle invasive bladder cancers and showed that chromatin modifier gene alterations occur in 75% of cases. Most of these alterations are predicted to result in loss of function; however, their effects on bladder cancer initiation, progression, and response to therapy are largely unknown. These genes alter the configuration of the DNA-histone interface, which affects the ability of DNA-binding proteins to access their target sequences. We hypothesize that chromatin modifier gene mutation leads to gene expression changes that support bladder cancer initiation and progression through enhancer disruption. Here, we test the hypothesis that KDM6A inactivation alters the chromatin state of urothelial cells and engenders a transcriptional program that results in neoplastic growth in a mouse model.