SWI/SNF (SWItch/Sucrose Non-Fermentable) is the most frequently mutated chromatin-remodelling complex in human malignancy, with over 20% of tumours having a mutation in a SWI/SNF complex member. Mutations in specific SWI/SNF complex members are characteristic of rare chemoresistant ovarian cancer histopathological subtypes. Somatic mutations inARID1A, encoding one of the mutually exclusive DNA-binding subunits of SWI/SNF, occur in 42–67% of ovarian clear cell carcinomas (OCCC). The concomitant somatic or germline mutation and epigenetic silencing of the mutually exclusive ATPase subunits SMARCA4 and SMARCA2, respectively, occurs in Small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT), withSMARCA4mutation reported in 69–100% of SCCOHT cases and SMARCA2 silencing seen 86–100% of the time. SomaticARID1Amutations also occur in endometrioid ovarian cancer (EnOC), as well as in the chronic benign condition endometriosis, possibly as precursors to the development of the endometriosis-associated cancers OCCC and EnOC. Mutation of theARID1AparalogueARID1Bcan also occur in both OCCC and SCCOHT. Mutations in other SWI/SNF complex members, includingSMARCA2,SMARCB1andSMARCC1, occur rarely in either OCCC or SCCOHT. Abrogated SWI/SNF raises opportunities for pharmacological inhibition, including the use of DNA damage repair inhibitors, kinase and epigenetic inhibitors, as well as immune checkpoint blockade.
SWI/SNF（SWItch/Sucrose Non-Fermentable）复合物是人类恶性肿瘤中最常发生突变的染色质重塑复合物，超过20%的肿瘤存在SWI/SNF复合物成员的突变。特定SWI/SNF复合物成员的突变是罕见化疗耐药性卵巢癌组织病理学亚型的特征性表现。编码SWI/SNF中互斥DNA结合亚基之一的ARID1A基因，其体细胞突变在42-67%的卵巢透明细胞癌（OCCC）中出现。在卵巢高钙血症型小细胞癌（SCCOHT）中，互斥的ATP酶亚基SMARCA4和SMARCA2分别伴随体细胞或种系突变及表观遗传沉默，其中SMARCA4突变在69-100%的SCCOHT病例中被报道，而SMARCA2沉默的发生率为86-100%。体细胞ARID1A突变也见于卵巢子宫内膜样癌（EnOC）以及慢性良性病变子宫内膜异位症中，可能作为子宫内膜异位症相关癌症OCCC和EnOC发展的前驱病变。ARID1A的旁系同源基因ARID1B的突变同样可发生于OCCC和SCCOHT中。其他SWI/SNF复合物成员（包括SMARCA2、SMARCB1和SMARCC1）的突变在OCCC或SCCOHT中较为罕见。SWI/SNF功能缺失为药物抑制提供了治疗机遇，包括使用DNA损伤修复抑制剂、激酶与表观遗传抑制剂，以及免疫检查点阻断疗法。
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