Rnf43 mutant mice showed gastric hyperproliferation (Neumeyer et al. Carcinogenesis 2019), that was exacerbated upon H. pylori infection (Neumeyer et al. Cancers 2019). More recently, we have demonstrated using in vitro and in vivo models the involvement of RNF43 in the DNA damage response in gastric cells (Neumeyer et al. Cell Mol Gastroenterol Hepatol. 2021). In a next step, we are analyzing the mutation status of RNF43 in human gastric tumor samples and studying these mutations functionally by introducing them in gastric cells using CRISPR/CAS9 technology. These studies will help us to determine how RNF43 mutations contribute to gastric carcinogenesis.