Additional exome sequencing studies revealed that specific cancers have mutations in different subunits of BAF complexes (Fig. 3). Many subunits do not have an elevated mutational rate in any tumor sequenced thus far and hence do not appear to contribute to tumor suppression. In some cases, this is because they are simply not expressed in dividing cells, as is true for the postmitotic, neuron-specific subunits, BAF53b, BAF45b, BAF45c, and CREST (SS18L1). However, in other cases, certain subunits that are ubiquitously expressed also appear to make no detectable genetic contribution to human cancer, but are physically located next to subunits that make extensive contributions. Indeed, this is the case with BAF53A, which is bound directly to BRG1. BRG1 is highly mutated in cancer, whereas BAF53A (ACTL6A) is not. However, the null phenotype for BAF53a is stronger than Brg, which might make it genetically less visible. Again, many of the subunits most highly mutated in cancer and human neurologic disease are not required for in vitro chromatin remodeling. The extensive genomic observations described above have placed a set of three constraints on
