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 activation could further reduce the activity of the BAF complex. However, the two mutations could cooperate by a completely different mechanism. For example, if the activation of PI3K leads to increased cell division in a cell lacking a BAF subunit, one would expect the consequent defect due to failure of TopoII function (97) (see below) to be sensitized. Activated PI3K would drive more “at-risk” cell divisions, leading to more mutations and advancement along the pathway to cancer. Another possibility would be that loss of BAF function leads to more point mutations and a greater likelihood of activation of PI3K. These possibilities can at least in part be resolved by understanding the time that the mutations occur during the course to cancer using allele frequency calculations.
