Therapeutically targeting aberrant chromatin remodeling in sarcomas

SNF5, a core subunit of the SWI/SNF chromatin remodeling complex, is a potent tumor suppressor that is specifically mutated in several types of sarcoma.  It has been thought that oncogenesis in the absence of SNF5 occurs due to a loss of function of the SWI/SNF complex.  However, based upon preliminary data we hypothesize that cancer instead arises due to oncogenic activation of the residual SWI/SNF complex.  We propose to utilize our genetically engineered mouse models to demonstrate this, to further establish that targeted inhibition of residual activity can be therapeutically beneficial, and to establish a pre-clinical model.