Re-assessing stem cells in the stomach—one story two tales

Gastric cancer is the third most common cancer worldwide, and it accounts for 3–10% of all cancer-related deaths. The vast majority (90–95%) of gastric cancers are adenocarcinomas which include two major histologic types, intestinal and diffuse. Although intestinal-type cancer has been associated with chronic atrophic gastritis and intestinal metaplasia, the exact mechanisms leading to cancer initiation and progression remain largely unknown. Stem/progenitor cell mutations have been linked to cancer initiation in multiple gastrointestinal organs including the esophagus, where we utilized lineage tracing to show that basal progenitor cells are the cell-of-origin for esophageal squamous cell carcinoma (1). By contrast, the cell-of-origin for gastric cancers remains somewhat controversial, in part due to the possible presence of multiple stem cells in the stomach (2-5).