English: The top panel shows that normal stem cells in adult intestinal cell epithelial renewal utilize the genes listed as epigenetic gatekeepers to control stem/progenitor cell proliferation and generate precursor cells which mature normally. When these genes are abnormally silenced, especially in groups, as shown in the colon polyps in the middle panel, this helps foster, abnormal, pre-invasive stem/progenitor cell expansion (red box showing neoplastic self-renewing cells), creating polyps and a cancer risk state. The risk state, as per the text, can foster oncogenic responses to key mutations which are labeled as the genetic gatekeepers. This combination of epigenetic and genetic abnormalities, and other recurring ones, can lead to invasive colon cancers built upon the self-renewing cells originally present and new ones created by the combination of molecular changes.