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A Potential Role of Neuroendocrine Tumor Gene MEN1 in Reserve Intestinal Stem Cell (rISC) Proliferation

Neuroendocrine Tumors (NETs) are rare, slow‐growing neoplasias that feature an excess of hormone‐producing endocrine cells. The occurrence of NETs has long been linked to loss‐of‐function mutations of the tumor suppressor gene, Men1, which encodes the transcription‐factor associating protein menin. Evidence suggests that cancers originate from stem cell populations that acquire driver mutations, resulting in tissue hyperplasia. In the intestine, the cell of origin and underlying mutations giving rise to Gastrointestinal NETs (GINETs) is unknown. The intestinal epithelium is renewed by two populations of stem cells (ISCs), one that actively proliferates (aISCs) and one that is a quiescent ‘reserve’ population (rISC). rISCs express high levels of the transcription factor, SOX9, and also exhibit stem cell as well as endocrine‐like gene expression profiles.