ARID1A基因突变或失表达介导肿瘤发生的机制及其在胃癌免疫治疗中的价值

AT丰富结合域1A（AT-rich interactive domain 1A，ARID1A）是染色质重塑复合体SWI/SNF（SWItch/Sucrose non-ferment-able）的一个亚基，它是所有肿瘤中突变最频繁的染色质调节因子之一，这些突变大部分是移码或无义突变。ARID1A是一个抑癌基因，它的突变或失表达可能从不同的途径导致肿瘤的发生发展。同时，ARID1A突变或表达缺失与胃癌程序性死亡受体-配体1（programmed cell death-ligand 1，PD-L1）高表达、EB病毒（Epstein-Barr virus，EBV）阳性、微卫星高度不稳定性（microsatellite insta-bility-high，MSI-H）、高肿瘤突变负荷（tumor mutation burden，TMB）及较多的肿瘤浸润淋巴细胞（tumor infiltrating lymphocytes，TILs）相关，且免疫检查点抑制剂（immune checkpoint inhibitors，ICIs）可以明显延长ARID1A缺失的肿瘤患者的无进展生存期。本文就ARID1A基因突变或失表达导致肿瘤发生可能途径及其与胃癌免疫治疗的关系进行综述。 

Mechanism of ARID1A mutations or loss of expression mediating tumorigenesis and its value in immunotherapy for gastric cancer

AT-rich interactive domain 1A (ARID1A) is a subunit of SWItch/Sucrose non-fermentable complexes and one of the most frequently mutated chromatin regulators in all types of tumors. Most of these mutations are frameshift or nonsense mutations. ARID1A is a tumor suppressor gene, and its mutation or loss of expression may lead to development and progression of neoplasia via different molecular pathways. ARID1A mutations or loss of expression is associated with high programmed cell death-ligand 1 (PD-L1) expression, Epstein-Barr virus (EBV) positivity, microsatellite instability-high (MST-H) status, high tumor mutation burden (TMB), and abundant tumor-infiltrating lymphocytes (TILs) in gastric cancer. Studies have found that immune checkpoint inhibitors can significantly prolong the progression-free survival of cancer patients with ARID1A deficiency. In this article, we review the possible pathways mediating ARID1A mutations or loss of expression leading to tumorigenesis and the relationship between ARID1A deficiency and immunotherapy response in gastric cancer.