These studies suggest that mutations in BAF subunits lead to the inability to resolve tangles at anaphase, with subsequent strand breakage and attempted repair of these breaks in the cytoplasm of the separating cells. This could generate potential oncogenic driving mutations that would contribute to the pathogenesis of the cancer. As mentioned above, this potential mechanism of tumor suppression must be examined in the light of the results of exome sequencing studies. First, the effect of BAF deletion on TopoII must be shown to be genetically dominant. Thus, we would expect that loss of a single allele of an oncogenic BAF subunit would lead to impairment of TopoII function. Second, the ultimate effect of TopoII dysfunction would be expected to result in tissue-specific lesions in DNA. This could happen if TopoII used different cleavage sites in different tissues, as would be consistent with the highly tissue-specific nature of deoxyribonuclease (DNase) sensitivity over the genome (118). Finally, we would expect that the effect of TopoII would not be seen in an in vitro transcription reaction using nucleosomal templates. Indeed, this is
