Tumors with mutations in BAF57 (SMARCE1) provide an illustrative example of both the remarkable tissue specificity and domain specificity of the tumorigenic actions of BAF complexes. For most cancers, rates of mutation of BAF57 are extremely low (yet breast cancers have about a 10 to 14% incidence of amplification). However, in non–NF2-driven multiple spinal meningiomas, nearly 100% of the tumors have mutations in this gene (83). These tumors are more aggressive than normal meningiomas, which are localized and can be cured by surgical resection. Clear cell meningioma spreads through the spinal cord and central nervous system (CNS), giving rise to a lethal metastatic-like state. However, they rarely metastasize to other tissues. This subunit has the capacity to bind cruciform structures in DNA and might be a source of sequence-specific architectural DNA binding; however, it is not known if this occurs in vivo. The DNA binding domain is a nonspecific HMG domain, and introducing a point mutation into this domain gives rise to a mouse that suppresses the endogenous alleles and a phenotype very much like the loss of the Brg
