抑癌基因PBRM1在肾细胞癌中的作用研究进展

Research progress on the tumor suppressor gene PBRM1 in renal cell carcinoma

肾癌作为一种常见的泌尿系统肿瘤,其发生、发展涉及一系列遗传学包括表观遗传学水平的改变,且病因复杂,有着高度的异质性。肾细胞癌是肾癌的最主要类型,而透明肾细胞癌(CCRCC)是肾细胞癌最常见的亚型。近期通过外显子测序发现,多溴蛋白1(PBRM1)基因(编码BAF180蛋白)在CCRCC中的突变率可高达40%。BAF180蛋白是SWI/SNF染色质重塑复合体中PBAF(polybromo-associated BRG1-associated factor)的特异组成亚基之一,不仅参与了PBAF复合物的形成,还可介导该复合物与DNA特定区域的结合,从而影响基因的转录、翻译等过程,表明PBRM1在肾细胞癌发生发展中扮演着十分重要的角色。该文对肾细胞癌的主要癌相关基因尤其是抑癌基因PBRM1的研究现状、分子机制及临床转化研究进展进行综述,以期为SWI/SNF与肾细胞癌及其他相关肿瘤的基础和临床转化研究提供参考。

Renal cancer,as a common urinary system tumor,its occurrence and development involve a series of genetic events including changes in the level of epigenetics.Its etiology is complex and highly heterogeneous.Renal cell carcinoma is the chief type of kidney cancer,while the clear cell renal cell carcinoma(CCRCC)is the most common subtype of renal cell carcinoma.Recently,exon sequencing revealed that the mutation rate of polybromo-1(PBRM1)gene in CCRCC can be as high as 40%.BAF180 protein,which is encoded by PBRM1 gene,is one of the specific subunits of the chromatin remodeling complex PBAF(polybromo-associated BRG1-associated factor),a type of SWItch/sucrose nonfermentable(SWI/SNF)complexes.It not only participates in the formation of PBAF complex,but also mediates the binding of the complex to specific DNA regions,thus affecting the gene transcription and translation processes,so indicates that PBRM1 plays an important role in the occurrence and development of renal cell carcinoma.The research status,molecular mechanism and clinical transformation of the major cancer related genes in CCRCC,especially the tumor suppressor gene PBRM1,were reviewed in present paper,in order to provide reference for the basic and clinical transformation research of SWI/SNF in renal cell carcinoma and other related tumors.