Cell culture studies on adenomatosis of the colon and rectum (ACR) suggested that the clinical phenotype, colonic adenomas which become malignant recognised as a single clinical entity, may not be entirely the result of a single dominant mutation. Of the dermal cultures containing both epithelioid and fibroblastic cells established from six affected subjects from six unrelated ACR families, four showed increased tetraploidy and two did not. Of similar cultures established from four affected subjects form families with ACR associated with sebaceous cysts in consecutive generations, three did and one did not have increased tetraploidy. Irrespective of the in vivo relationship of increased tetraploidy to colonic cancer, the cultures from seven ACR patients had populations of tetraploid cells, at least in vitro, with chromosome instability. Such a difference in expression of the ACR genotype in vitro suggested genetic heterogeneity within this clinically defined group.
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