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Chunk #24 — PRE-GENOMICS: EARLY LINKS TO HUMAN CANCER

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Mammalian SWI/SNF chromatin remodeling complexes and cancer: Mechanistic insights gained from human genomics.
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Early studies found that malignant cell lines often had lost critical subunits of mSWI/SNF or BAF complexes, indicating that these complexes were likely to be tumor suppressors. In addition, they were found to bind the RB protein and repressed E2F function (59, 60). Definitive evidence that they were tumor suppressors came from the work of Versteege and colleagues, who found that BAF47 (INI1, hSNF5, SMARCB1) was uniformly lost in a rare childhood cancer known as malignant rhabdoid tumor (MRT). In these tumors, most often, germline loss of one allele is followed by loss of the second allele in the tumor tissue (rhabdoid predisposition syndrome), indicating that mutations in BAF47 behave as classic tumor suppressors with genetics similar to that of retinoblastoma (61). Additional early studies by Reisman and colleagues (62) discovered cell lines with inactivation of both Brg and Brm, such as the SW13 line. These studies were confirmed by Wong and colleagues (63), who found that several breast cancer cell lines had lost both Brg and Brm at the protein level but seemed to have mutations in only one