CLONALITY OF DYSPLASTIC EPITHELIUM IN COLORECTAL ADENOMAS FROM FAMILIAL ADENOMATOUS POLYPOSIS PATIENTS

Loss of function of both alleles of the APC gene results in colorectal adenoma formation in familial adenomatous polyposis, an autosomal dom inant genetic disorder leading to multiple colorectal tumors at an ear ly age, Previous molecular studies indicate that the mutant cells form ing dysplastic epithelium within adenomas are clonally derived, We sho w, using immunostaining and molecular techniques, that the dysplastic epithelium of adenomas actually contains a mixture of cells derived fr om both mutant and normal stem cells, Well-differentiated mucous cells in the dysplastic epithelium, one of the indicators of severity of dy splasia, were derived from normal stem cells, Carcinomas in these pati ents, in contrast, contained only mutant cells, indicating that the su bsequent mutations incurred by these cells have led to their isolation from the normal population.