Proteomic and Bioinformatic Analysis of mSWI/SNF (BAF) Complexes Reveals Extensive Roles in Human Malignancy
By Cigall Kadoch, D. Hargreaves, Courtney Hodges, Laura Elias, Lena Ho, J. Ranish, G. Crabtree. Nature Genetics, 2013
1,280 citations recorded by the source corpus.
Subunits of mammalian SWI/SNF (mSWI/SNF or BAF) complexes have recently been implicated as tumor suppressors in human malignancies. To understand the full extent of their involvement, we conducted a proteomic analysis of endogenous mSWI/SNF complexes, which identified several new dedicated, stable subunits not found in yeast SWI/SNF complexes, including BCL7A, BCL7B and BCL7C, BCL11A and BCL11B, BRD9 and SS18. Incorporating these new members, we determined mSWI/SNF subunit mutation frequency in exome and whole-genome sequencing studies of primary human tumors. Notably, mSWI/SNF subunits are mutated in 19.6% of all human tumors reported in 44 studies. Our analysis suggests that specific subunits protect against cancer in specific tissues. In addition, mutations affecting more than one subunit, defined here as compound heterozygosity, are prevalent in certain cancers. Our studies demonstrate that mSWI/SNF is the most frequently mutated chromatin-regulatory complex (CRC) in human cancer, exhibiting a broad mutation pattern, similar to that of TP53. Thus, proper functioning of polymorphic BAF complexes may constitute a major mechanism of tumor suppression.
Subfields: Molecular Biology, Oncology, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/ad189258ce4ae816556ae19e3be9695adbe71f54
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Citations in the corpus
- Mammalian SWI/SNF chromatin remodeling complexes and cancer: Mechanistic insights gained from human genomics (2015, background): “With more than 20% of human cancers bearing a mutation to one subunit of a 15-subunit complex (3, 4), mechanistic studies that translate the meaning of these genetic perturbations are critical for understanding oncogenic function.”
- Histone Modifications and Cancer. (2016, background): “BRD7 and, more recently, BRD9 bromodomain proteins have been identified as components of chromatinremodeling switch/sucrose nonfermenting (SWI/SNF) complexes, increasingly found to be mutated in a variety of human cancers (Kaeser et al. 2008; Kadoch et al. 2013).”
- Mechanisms and Functions of ATP-Dependent Chromatin-Remodeling Enzymes (2013, neutral): “…enzymes including Chd1, Chd4, and ATRX and other chromatin-related factors are also Endometrial cancer 17% Chd4 a See Garraway and Lander (2013) and Kadoch et al. (2013). detected in a range of cancers and in a range of albeit reduced frequency in comparison to SWI/SNF components (Garraway and…”
- ATP-dependent chromatin remodeling during mammalian development (2016, background): “…lymphoma family of proteins, such as BCL7A-C, BCL11A,B and bromodomain-containing proteins BRD7,9) and found to be part of stable BAF complexes (Kadoch et al., 2013; Kaeser et al., 2008), analyzing the function of these subunits in in vitro biochemical assays and via in vivo genetic…”