These discoveries have led to a search for tissue-specific and/or instructive roles for other chromatin remodeling and histone modification complexes. These studies and the finding that minor changes in subunit composition could result in malignancy (see below) put forward the understanding that biologic specificity likely emerged from subunit composition as the means of diversification of function or dysfunction (36, 48). With the view that cancer is development gone wrong, BAF250B (ARID1B) (one of three genes that occupy this position in BAF complexes) was recently found by trio and quad sequencing (mother, father, normal sib, and affected sib) to be the most frequently mutated gene in human neurodevelopmental disorders (58). Here also, the (heterozygous) mutations are generally dominant, implying that a dosage-sensitive process also underlies the developmental roles as well as the role in oncogenesis.
