Accumulation of Somatic Mutations in TP53 in Gastric Epithelium With Helicobacter pylori Infection

摘要: Background & Aims Helicobacter pylori infection is a risk factor for gastric cancer. To explore the genetic basis of cancer that develops in inflamed mucosa, we investigated aberrations latently accumulate nontumorous epithelium with H infection. Methods We performed whole-exome sequencing tumors, noncancerous tissues gastritis, and peripheral lymphocytes from 5 patients. additional deep-sequencing analyses selected tumor-related genes using 34 gastritis mucosal samples patients with or without also deep mice express transgenic human TP53 constitutively activation-induced cytidine deaminase (AICDA or AID) (human TP5 3 knock-in/AID-transgenic mice). Results Whole-exome revealed somatic mutations accumulated various tissues. Additional regions confirmed nonsynonymous low-abundance 15 cases (44.1%) ARID1A (14.7%). The –induced as well were predominantly C:G>T:A transitions GpCpX motifs—a marker deamination induced by AID. Constitutive expression AID mucosa led to , at amino acid coding positions identical those detected cancers. Conclusions Studies tumors humans indicate Increased activity these appears promote accumulation might carcinogenesis