Abstract 3639: ARID1 mutations may serve as a predictor of MSI and TMB levels in gastric cancer

Abstract

Abstract Background: ARID1A is a gene that produces a protein called BAF250a, which is a component of the chromatin remodeling complex. This complex plays a critical role in regulating gene expression by altering the structure of chromatin. ARID1A mutations and MSI-H are mutually exclusive in endometrial cancer, but not in ovarian cancer. ARID1A mutations are associated with high TMB in certain types of cancer, such as endometrial and gastric cancer. The relationship between ARID1B mutations and MSI-H/TMB is complex, and this study aims to clarify it in gastric cancer. Methods: The formalin-fixed paraffin-embedded (FFPE) tissues 337 patients with gastric cancer who have underwent next-generation sequencing (NGS) include 733 genes from Nov, 2019 to Mar, 2023 in 3DMed Clinical Laboratory Inc. were investigated in this study. These patients are still being followed up. Result: In this study, 337 patients with gastric cancer were analyzed for ARID1A and ARID1B mutations, MSI-H status, and TMB levels. The results showed that 17.8% of the patients had ARID1A mutations, 8.9% had ARID1B mutations, and 3.6% had both mutations. Additionally, 7.7% of the all patients had MSI-H. The study found that patients with ARID1 mutations had significantly higher rates of MSI-H compared to unselected patients. Specifically, 35% of patients with ARID1A mutations, 30% with ARID1B mutations, and 75% with both mutations had MSI-H, compared to 7.7% in unselected patients. Furthermore, TMB levels were higher in patients with ARID1A or ARID1B mutations compared to wild-type and unselected patients (p<0.0001). There was no significant difference observed between patients with ARID1A and ARID1B mutation subgroups in terms of TMB levels (p = 0.3515). However, TMB levels were lower in patients with ARID1A or ARID1B mutations compared to patients with both mutations (p = 0.0036, p = 0.0104). These findings suggest that ARID1 mutations may cause genomic and chromosomal instability in gastric cancer, leading to higher rates of MSI-H and TMB. Conclusion: The study highlights the potential clinical significance of ARID1 mutations as a biomarker for predicting MSI-H and TMB levels in gastric cancer, which could help guide personalized treatment strategies for patients with this disease. However, further research is needed to confirm these findings and to determine the clinical implications of ARID1 mutations in gastric cancer. Citation Format: Chunsheng Xu, Bo Lian, Yujie Dai, Weiming Duan, Feilong Zhao, Mengbin Li. ARID1 mutations may serve as a predictor of MSI and TMB levels in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3639.