Different gene mutations among gastric cancer patients with MSS and MSI-H types in China.

e16018 Background: Gastric cancer is one of the leading causes of cancer-related deaths worldwide, although the incidence has gradually decreased in many Western countries. The status of microsatellites is an important biomarker of gastric cancer immunotherapy, but not all patients with MSI-H have excellent curative effect. Therefore, this study of the molecular background of MSS and MSI-H, which is helpful for the development of gastric cancer immunotherapy in Chinese patients. Methods: The formalin-fixed paraffin-embedded (FFPE) tissues of 6603 patients with CRC who have underwent next-generation sequencing (NGS) from Jan, 2019 to Apr, 2021 in 3DMed Clinical Laboratory Inc. were investigated in this study. These patients are still being followed up. Statistical analysis was performed using Microsoft Office Excel (2013). Results: 7.0% (139/1997) patients with MSI-H status, MSI-H and MSS tumors showed striking gene mutation differences. Among the 10 genes with the highest mutation rate, TP53 ERBB2 CDH1 PIK3CA mutations appear in both MSI-H and MSS patients. But the mutation rates of these genes vary greatly (32.3% VS 53.7%, 19.4% VS 13.0%,12.2% VS 8.2%, 34.5% VS 8.2%, respectively). Among the top 10 mutated genes, ARID1 (70.5%), mutation with the highest rate is only mutated in MSI-H patients. There are other gene mutations, including KMT2C (68.3%), RNF43 (59.7%), TGFBR2 (58.3%), RNF43 (34.5%), MSH3 (46.8%), RAD50(41.0%), MSH6(31.7%), ATR (30.2％), which have hugely higher mutation rates than MSS patients. It is worth noting that the mutation rate of TP53, BCL2L11, CYP2C19, MYC, CCNE1 and UGT1A1 in MSS patients is absolutely higher than that in MSI-H. Conclusions: There are completely differences in gene mutations between MSI-H and MSS gastric cancer patients in the Chinese population, especially TP53, ERBB2, CDH1, PIK3CA KMT2C, RNF43, TGFBR2, RNF43, MSH3, RAD50, MSH6 and ATR, which are of great significance for accurate patient stratification and treatment.