top down model
One of two proposed morphologic pathways of spontaneous development of adenomas. The top-down model is based on observations of dysplastic cells only located at the luminal surface of the crypts along with migration of adenomatous cells from the surface to the base of a crypt. In this model, an initial stem cell mutation is thought to occur in the epithelial mucosa situated in the intra-cryptal zone, between 2 crypt orifices, with subsequent stem cell division producing a mutant clone that expands laterally and downwards into the crypt, displacing normal epithelial cells.
Analysis of 4 single-nucleotide polymorphisms (SNP) within the APC gene in tissue from sporadic adenomas showed loss of heterogeneity (LOH) of APC and high proliferation activity in cells in the upper part of the crypts, but not in the histologically normal crypt bases. This suggests that the stem cell could be located in the intra-cryptal zone or, if located in the base of the crypt, the APC mutation in the stem cell would prevent its terminal differentiation and change in migration dynamics, allowing it to remain in the mucosa before expanding laterally and downwards.
Reference Rikke Dalgaard Hansen, U Copenhagen, PhD thesis 31.07.2007