||Helicobacter pylori (H. pylori) infection and the resultant chronic gastric inflammation is an important etiologic factor for gastric cancer development. To explore the genetic basis of gastric cancer that developed in the inflamed gastric mucosa, we investigated genetic aberrations latently accumulated in non-tumorous chronically inflamed gastric epithelium. Whole exome sequencing on 5 matched pairs of gastric cancer and non-cancerous gastritis tissues in patients with H. pylori infection clarified that somatic mutations were accumulated in various genes in inflamed gastric tissues. Additional deep sequencing analyses on the tumor-related genes including TP53, ARID1A, CTNNB1, PIK3CA, MLL2 and SUV39H1 were performed in H. pylori-related gastritis mucosa in 23 patients with gastric cancer and 6 patients without gastric cancer. By deep sequencing, non-synonymous mutations on gastritis mucosa of 23 patients with gastric cancer were detected in TP53 in 9 cases (39.1%), ARID1A in 2 cases (8.7%), and MLL2 in 2 cases (8.7%), as well as non-synonymous mutations on gastritis mucosa of patients without gastric cancer were detected in TP53 in 4 cases (66.7%) and ARID1A in 1 cases (16.7%). Interestingly, not only mutations in gastric cancer genomes but also TP53 mutations in H. pylori-inflamed gastritis mucosa were predominantly C:G>T:A transitions in the context of GpCpX or ApCpX, mutation signatures invloved in activation-induced cytidine deaminase (AID) activity. Furthermore, in vivo studies with human TP53 knocked-in mice model revealed that constitutive AID expression in gastric mucosa caused the generation of TP53 mutations whose positions were hot spots in human gastric cancers. These findings provide novel evidence that somatic mutations were latently accumulated in various genes in inflamed gastric mucosa with H. pylori infection. The genetic alterations accumulated in TP53 gene of the gastritis mucosa would provide a putative genetic basis for the increased susceptibility to gastric carcinogenesis in patients with H. pylori infection.