最近我们在国际上首次发现SWI/SNF染色质重塑复合物亚基BRM在40％低分化肾透明细胞癌中失活。在既有高分化又有低分化区域的复合性肿瘤内，BRM缺失仅位于差分化区域。进一步测序发现，BRM编码区仅有少量同义突变。我们推测BRM缺失对肿瘤进展起重要作用，其失活机制是可逆的表观遗传学沉默，可被组蛋白去乙酰化酶（HDAC）抑制剂复表达，有靶向治疗前景。HDAC包含18个亚型，而针对多个HDAC亚型的广谱HDAC抑制剂除了可以诱导BRM表达外还可以通过C末端乙酰化使得BRM蛋白失活。因此明确具有诱导BRM作用的HDAC亚型，对肿瘤的靶向治疗至关重要。本研究继续明确BRM在肾透明细胞癌的失活机制，通过对肾小管上皮细胞及肾透明细胞癌细胞系中相关基因的干预，在体内外进行正反方面相关蛋白或分子的功能机制研究，明确其对肿瘤进展的作用，明确具体起诱导作用的HDAC亚型。结合基因表达谱探索BRM的影响机制。

Recently, we first identified loss of SWI/SNF complex subunit BRM expression as a frequently observed event (40%) in poorly differentiated clear cell renal cell carcinoma (RCC). Staining for BRM was only negative in the poorly differentiated regions of composite RCCs which also harbor an admixed typical low-grade component. After exome sequencing, only a few samesense mutation were found in coding region for BRM gene. Together with other findings in the literatures, it is reasonable to speculate that a loss of BRM expression may play an important role during tumor progression and is due to reversible epigenetic silencing that could be restored using Histone deacetylases (HDACs) inhibitors. Currently, 18 HDACs have been identified in humans. BRM has been shown by several laboratories to be readily induced as well as inactivated via acetylation following treatment with pan-HDAC inhibitors. It is important for targeting therapy to determine which specific HDACs regulate BRM. In this study, we further explore the mechanism of loss of BRM expression in clear cell RCC using FISH, reverse transcriptase PCR, DNA sequencing or other molecular methods. We study the pathogenic mechanism of BRM by related gene intervention in vitro and in vivo model and identify its important role during tumor progression and the targets for the restoration and reactivation of BRM.