Epithelial cells lining the mature @entity1 colon do not normally express receptors for @entity6501 ( @entity37358 ). In contrast, we have shown that when aberrantly expressed in functional form in @entity694 , this protein acted as a morphogen where it caused @entity5 cells to adopt a better-differentiated phenotype. Importantly, @entity37358 mRNA is ubiquitously mutated in @entity1 @entity694 cell lines, with inactivating mutations detected in all cell lines not expressing functional receptor. Since @entity694 are heterogeneously differentiated, we set out to determine if the @entity37358 gene was mutated as a function of @entity5 cell differentiation in archived @entity1 @entity694 . We used laser capture microscopy to dissect out 67 regions of defined differentiation from 20 @entity1 @entity694 randomly selected from the UIC @entity5 Bank. Except for two polymorphisms, the @entity37358 gene was not mutated in nonmalignant epithelial cells. In contrast, 42 distinct mutations were identified in malignant cells. Overall mutation number inversely correlated with the degree of @entity5 cell differentiation. Within any @entity5 , all @entity37358 mutations found within better-differentiated cells were conserved in more poorly-differentiated cells; while all poorly-differentiated cells contained mutations resulting in @entity37358 pharmacological inactivation. These data suggest that accumulation of mutations within the @entity37358 gene ultimately resulting in the production of nonfunctional receptors may represent a previously unappreciated mechanism allowing for the dedifferentiation of @entity5 cells within any particular @entity694 ; and that poorly-differentiated @entity5 cells within any individual @entity5 may arise clonally from their better-differentiated precursors.

Increased frequency of @entity37358 gene mutations during XXXX .

@entity1 :: ('9606', 'Species') :: ['human'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'GI Tumor', 'cancer'] @entity37358 :: ('2925', 'Gene') :: ['GRPR'] @entity6501 :: ('2922', 'Gene') :: ['gastrin-releasing peptide'] @entity694 :: ('MESH:D003110', 'Disease') :: ['colon cancer', 'colon cancers']
@entity694 :: (MESH:D003110,Disease) :: ['colon-adenocarcinoma progression']
