though yielding a different type of tumor, likely has a similar pathogenesis. BAF complexes in the mutant cells are unable to remove Polycomb complexes and their histone modification, H3K27Me3, from the Ink4a (Cdkn2a) locus, which normally suppresses proliferation (69). The genomes of MRTs are devoid of mutations outside of SMARCB1 loss and are estimated to have the lowest mutational burden of any human tumor sequenced to date (71). Thus, the tumors seem to be induced exclusively by changes in epigenetic regulation (except for the initiating mutations in BAF47). The mechanism by which loss of BAF47 leads to a failure to remove Polycomb is unclear and suggests that one of the important roles of BAF complexes is to oppose Polycomb as indicated from studies in flies and mammals (8, 11).
