Road of no return - loss of TP53 paves a defined evolution path from gastric preneoplasia-to-cancer

Gastric cancer (GC), the fifth- and fourth-leading causes of morbidity and mortality worldwide, still lacks effective diag-noses and treatment. Moreover, China accounts for nearly 50％ of the newly diagnosed and death cases of GC globally1. Being directly exposed to external food intake, extremely acidic content, and microorganisms, such as Helicobacter pylori and Epstein-Barr virus (EBV), stomach homeostasis is easily per-turbed and disrupted. Importantly, the gastric epithelium is composed of multiple cell types, including chief, parietal, pit, and stem cells. The lineages of these gastric epithelial cells are rather plastic, giving rise to a high degree of GC heterogeneity. To date, the complex pathology of GC is poorly understood, especially with respect to the cellular origin, initiation, and molecular evolution of GC, which thwarts efforts to develop strategies for preventing, monitoring, and treating GC2.