Molecular Pathways Molecular Pathways : SWI / SNF ( BAF ) Complexes Are Frequently Mutated in Cancer — Mechanisms and Potential Therapeutic Insights
Molecular Pathways Molecular Pathways : SWI / SNF ( BAF ) Complexes Are Frequently Mutated in Cancer — Mechanisms and Potential Therapeutic Insights
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发表时间：
2013
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通讯作者：
Xiaofeng Wang;Jeffrey R. Haswell;C. Roberts
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作者：
Xiaofeng Wang;Jeffrey R. Haswell;C. Roberts
SWI/SNF染色质重塑复合物是一种多形多亚基细胞机器，它利用ATP水解的能量来调节染色质结构。复合物与转录因子在启动子和增强子处相互作用以调节基因表达并有助于谱系特化、分化和发育。SWI/SNF复合物在肿瘤抑制中的作用的最初线索来自十多年前，当时发现编码SMARCB 1/SNF 5核心亚基的基因在几乎所有儿科横纹肌样肿瘤中特异性失活。在过去的三年中，癌症基因组测序工作揭示了SWI/SNF亚基基因的高突变率，这些基因在20%的人类癌症中集体突变，接近p53突变的频率。在这里，我们提供了这些新认识的肿瘤抑制复合物的背景，讨论了肿瘤抑制活性的机制，并强调可能导致SWI/SNF突变型癌症的潜在治疗靶点的发现。临床癌症研究; 20（1）; 21-27。2013年AACR。
SWI/SNF chromatin remodeling complexes are pleomorphic multisubunit cellular machines that utilize the energy of ATP hydrolysis to modulate chromatin structure. The complexes interact with transcription factors at promoters and enhancers to modulate gene expression and contribute to lineage specification, differentiation, and development. Initial clues to a role in tumor suppression for SWI/SNF complexes came over a decade ago when the gene encoding the SMARCB1/SNF5 core subunit was found specifically inactivated in nearly all pediatric rhabdoid tumors. In the last three years, cancer-genome sequencing efforts have revealed an unexpectedly highmutation rate of SWI/SNF subunit genes, which are collectivelymutated in 20%of all human cancers and approach the frequency of p53mutations. Here, we provide a background on these newly recognized tumor suppressor complexes, discuss mechanisms implicated in the tumor suppressor activity, and highlight findings that may lead to potential therapeutic targets for SWI/SNFmutant cancers. Clin Cancer Res; 20(1); 21–27. 2013 AACR.