Figure 6From: The overmethylated genes in Helicobacter pylori-infected gastric mucosa are demethylated in gastric cancers Schematic diagram of the adaptive differentiation and neoplastic transformation of newly fixed stem cells. In the newly fixed stem cells in the gastric mucosa, the gene-adjacent retroelements (R) drive the concurrent methylation of CpG-island genes in a distance-dependent manner. Given the interaction of the stomach-specific genes lacking CpG-islands and the housekeeping genes containing CpG-islands, which share the limited amount of nuclear proteins in a nuclear space, the overmethylation of CpG-islands down-regulates the housekeeping genes and up-regulate the stomach-specific genes. A high expression of stomach-specific genes promotes the non-dividing terminal differentiation of newly fixed stem cells in the stomach tissue-environment. The LOH events reducing a gene dose lead to 1) dose-compensatory demethylation, 2) the interruption of terminal differentiation, and 3) reactivation of a stem-cell intrinsic program for cell migration. Additionally, the highly expressed stomach-specific genes are overmethylated in a subset of gastric cancers and the overmethylated genes facilitate the interruption of terminal differentiation.Back to article page