The advent of exome sequencing made it possible to not only identify recessive tumor suppressors but also identify mutations in genes that tend to co-occur with them, pointing toward potential mechanisms and therapeutic approaches. When BAF250A (ARID1A) mutations were first identified in ovarian cancer, it was immediately clear that cooperating mutations in phosphatidylinositol 3-kinase (PI3K) were frequent. This trend became even more clear as additional mutations were found in Brg and other subunits. The association seems invariably to be an activating mutation in PI3K with a loss of function in one of the BAF subunits, most commonly BAF250a or BAF250b. This is intriguing for a number of reasons. First, activation of PI3K should deplete the supply of PIP2 (phosphatidylinositol 4,5-bisphosphate) by phosphorylation on the 3′ position of the inositol ring, giving rise to phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3]. PIP2 binds the BAF complex to one site on the Brg subunit, near the ATPase domain (96). As yet, the significance of this binding is unclear, but it may regulate the activity of BAF complexes and their association with chromatin (47), and hence, PI3K
