BAF250b is the most commonly mutated gene discovered in a recent exome sequencing study of human developmental diseases (58), and Brm is mutated in and causes a number of human neurodevelopmental diseases (43). Thus, therapeutic targeting of Brm or BAF250b in human cancer may have inherent toxicity. In addition, many tumors show genetic inactivation of one subunit and epigenetic inactivation of the homolog. For example, SW13 and several other cell lines contain a mutation in Brg, but do not express Brm, presumably by epigenetic inactivation (59, 62). In addition, a number of tumors have lost both BAF250a and BAF250b. Again, the mechanism appears to be genetic inactivation of one subunit and epigenetic suppression of the homologous subunit. It is not clear what allows the cell to compensate for the loss of both Brg and Brm or BAF250a and BAF250b, but this mechanism might be an additional susceptibility that would provide more lasting therapeutic effect than inhibition of one paralogous subunit but not the other.
