When exon sequencing studies of human cancer began in 2010, a more complicated genetic picture emerged. The remainder of this review focuses in large part on the nature of these mutations and their possible mechanisms. Initial reports showed that about 57% and 46% of ovarian clear cell carcinomas and endometriosis-associated ovarian carcinomas, respectively, contained inactivating mutations, distributed along the length of the BAF250A (ARID1A) subunit (45, 64). Nearly all of these cases had mutations in only a single allele, indicating that BAF250A might be a dominant tumor suppressor subunit within the complex. These initial studies were confirmed repeatedly, indicating that somehow the loss of a single allele of a single subunit contributed to the pathogenesis of ovarian cancer (65). About this same time, studies of an unusual intellectual disability condition (Coffin-Siris syndrome) characterized by difficulty with language acquisition and mental retardation found mutations in BAF250B (ARID1B), which were also heterozygous in most cases. Because the issue of tumor heterogeneity can often inaccurately skew the determination of whether one or both alleles are inactivated, the discovery of the heterozygous BAF250B mutations
