PMS2
小结
PMS2是抑癌基因，编码蛋白是一种内切核酸酶，在错配修复（MMR）通路中起着至关重要的作用。PMS2使DNA产生缺口以启动错配链的切除。PMS2的突变导致无法正确修复DNA中的错配和插入/缺失环，这增加了肿瘤高度突变和微卫星不稳定性高（MSI-H）表型。PMS2的胚系突变可引起Lynch综合征，其易患某些癌症，包括结直肠癌、子宫内膜癌和卵巢癌。散发性PMS2突变也在许多组织类型的癌症中有所报道。
PMS2 encodes a tumor suppressor involved in DNA mismatch repair. Germline mutations of PMS2 are associated with Lynch Syndrome and predispose to colorectal cancer. PMS2 is an endonuclease that plays an essential role in the mismatch repair (MMR) pathway. Specifically, PMS2 nicks DNA to initiate excision of a mismatched strand. Mutations in PMS2 lead to an inability to correctly repair mismatches and insertion/deletion loops in the DNA, which results in increased tumor hypermutation and a microsatellite instability high (MSI-H) phenotype. Germline mutations of PMS2 can cause Lynch syndrome, which predisposes to certain cancers including colon, endometrial and ovarian cancers and implicates PMS2 as a tumor suppressor. Sporadic PMS2 mutations have also been reported in cancers from numerous tissue types. Tumor hypermutation has been associated with response to certain immunotherapies. Specifically, pembrolizumab has been FDA approved for all MMR-deficient and MSI tumors, irrespective of specific tumor etiology.