The genetic alteration spectrum of the SWI/SNF complex: The oncogenic roles of BRD9 and ACTL6A

SWItch/Sucrose NonFermentable (SWI/SNF) is a set of multi-subunits chromatin remodeling complexes, playing important roles in a variety of biological processes. Loss-of-function mutations in the genes encoding SWI/SNF subunits have been reported in more than 20% of human cancers. Thus, it was widely considered as a tumor suppressor in the past decade. However, recent studies reported that some genes encoding subunits of SWI/SNF complexes were amplified and play oncogenic roles in human cancers. In present study, we summarized the genetic alteration spectrum of SWI/SNF complexes, and firstly systematically estimated both the copy number variations and point mutations of all 30 genes encoding the subunits in this complex. Additionally, the bioinformatics analyses were performed for two significantly amplified genes, ACTL6A and BRD9, to investigate their oncogenic roles in human cancers. Our findings may lay a foundation for the discovery of potential treatment targets in SWI/SNF complexes of cancers.

SWI/SNF复合物（SWItch/Sucrose NonFermentable）是一类多亚基染色质重塑复合物，广泛参与多种生物学过程。编码SWI/SNF亚基的基因出现功能丧失性突变的情况，在超过20%的人类癌症中均有报道，因此在过去十年间，该复合物被广泛认定为肿瘤抑制因子。然而近期研究表明，部分编码SWI/SNF复合物亚基的基因发生扩增，并在人类癌症中发挥致癌作用。本研究系统梳理了SWI/SNF复合物的遗传变异谱，并首次针对该复合物全部30个编码亚基的基因，全面评估了其拷贝数变异与点突变情况。此外，我们针对两个显著扩增的基因ACTL6A与BRD9开展了生物信息学分析，以探究二者在人类癌症中的致癌作用。本研究结果可为癌症中SWI/SNF复合物潜在治疗靶点的发掘奠定理论基础。