SMARCB1
小结
SMARCB1 是抑癌基因，编码蛋白认为是SWI/SNF染色质重塑复合物的一种核心亚基。SWI/SNF复合物对于人的正常发育是重要的，并且是细胞分化期间转录程序转变所必需的。在癌症中，SMARCB1作为一种强的肿瘤抑制因子。该基因在横纹肌样肿瘤、家族性神经鞘瘤、小细胞肝母细胞瘤、骨骼外黏液样软骨肉瘤、未分化肉瘤、上皮肉瘤、脑膜瘤和低分化脊索瘤中发生突变。Rhabdoid predisposition 综合征的患者中检测到SMARCB1杂合胚系突变，并在之后的肿瘤发生中伴随等位基因的缺失。最近发现，SMARCB1突变细胞依赖于PRC2组分EZH2，这促使EZH2抑制剂在SMARCB1突变型癌症患者中的开展临床试验。
SMARCB1 (INI1, BAF47, SNF5) is present in all known variants of the SWI/SNF chromatin remodeling complex, and is thus considered a core subunit. SWI/SNF complexes are ATP dependent nucleosome remodelers which are required for efficient accessibility of genes to the transcriptional machinery . SWI/SNF complexes are important for normal human development and are required for the transition of transcriptional programs during cellular differentiation. In cancer, SMARCB1 acts as a strong tumor suppressor. It is mutated in rhabdoid tumours, familial schwannomatosis, small-cell hepatoblastomas, extraskeletal myxoid chondrosarcomas, undifferentiated sarcomas, epitheliod sarcomas, meningiomas and poorly differentiated chordomas. Heterozygous SMARCB1 mutations are found in patients with rhabdoid predisposition syndrome, which is characterized by the inheritance of a defective SMARCB1 allele followed by the loss of the remaining allele in the tumours. Mouse models of SMARCB1 mutations recapitulate the tumor suppressor functions observed in humans. The exact mechanism by which SMARCB1 loss leads to malignant transformation is not yet well understood, however, expression analyses have shown that one consequence of SMARCB1 loss is the activation of gene expression programmes that are associated with proliferation and dedifferentiation. Recently, it was found that SMARCB1 mutant cells depend on the PRC2 component EZH2 which has lead to clinical trials of EZH2 inhibitors in patients with SMARCB1 mutant cancers.