Mutations of adenomatous polyposis coli (APC) gene are uncommon in sporadic desmoid tumours

Abstract

Summary Desmoids are locally aggressive. non-metastasizing soft-tissue tumours. whose aetiology is still unclear. In patients affected with familial adenomatous polyposis (FAP), the incidence of desmoids is much higher than in the general population. The

Predominance of beta-catenin mutations and beta-catenin dysregulation in sporadic aggressive fibromatosis (desmoid tumor)

“…Previous work, demonstrating that it is a monoclonal lesion, suggests that it is caused by a mutation giving a proliferative advantage to the involved cells (Alman et al, 1997b;Li et al, 1996). Studies showing that somatic APC mutations are present in a subset of sporadic lesions, suggest that APC plays a role deregulating growth control in the lesion (Alman et al, 1997a;Giarola et al, 1998). This study shows that most lesions, that do not harbor APC mutations, contain a mutation in beta-catenin, resulting in a stabilized protein product.…”

“…The incidence of somatic APC mutation varies widely between the two previous reports (Alman et al, 1997a;Giarola et al, 1998). Our initial report of APC mutations in aggressive ®bromatosis studied a relatively small number of tumors, and the high incidence found was likely due to a sampling error from examining only this small number.…”

“…It occurs as a sporadic lesion, or as part of the familial conditions, familial adenomatous polyposis (FAP) and familial in®ltrative ®bromatosis, which are both caused by germ-like mutations in the adenomatous polyposis coli (APC) gene (Eccles et al, 1996;Kinzler et al, 1991). We, and others, found somatic APC mutations in a subset of sporadic aggressive ®bromatoses (Alman et al, 1997a;Giarola et al, 1998). One function of the APC gene product is to regulate the cellular level of beta-catenin, which acts in cell adhesion, and is also a mediator in Wnt (Wingless) signaling pathway (Behrens et al, 1998;Papko et al, 1996).…”

Estrogen receptor‐β expression in extraabdominal fibromatoses

“…Rather than mutations of the APC gene, most cases of sporadic fibromatosis are associated with mutations of the ␤-catenin gene that inhibit its degradation. 32,33 Superficial fibromatoses appear to have mutations of neither gene, but have a lesser degree of nuclear ␤-catenin accumulation, indicating a possible role of abnormal ␤-catenin regulation in those lesions, and indicating a role for an APC‫-␤گ‬catenin‫گ‬wnt pathway signaling in most cases of fibromatosis. 34 Evidence for interaction of the estrogen receptor pathway with the APC beta catenin pathway is circumstantial.…”

Superficial Fibromatoses are Genetically Distinct from Deep Fibromatoses

“…This observation has led to the study of APC mutations in sporadic desmoid tumors. Because one function of the APC gene involves regulation of the cellular level of ␤-catenin, the interaction between these two molecules has been explored in tandem, and although sporadic desmoid tumors may have APC mutations (16,17), they are more likely to have ␤-catenin mutations (18,19). It appears that the majority of desmoid tumors, both familial and sporadic, have mutations of one of these two genes.…”