Novel mutations and inactivation of both alleles of the APC gene in desmoid tumors

Desmoids are non-metastasizing fibroblastic tumors which invade locally and tend to recur after surgical excision. They are rare in the general population, but occur with a significant frequency in familial adenomatous polyposis (FAP), an un-common autosomal dominant disease, characterized by mul-tiple adenomas of the colorectum (1—4). Germ-line mutations inactivating one allele of the adenomatous polyposis coli (APC) gene are responsible for FAP (5-9). According with Knudson's 'two-hit ' theory (10), inactivation of the residual allele of the APC gene is a critical step in the molecular pathogenesis of colorectal adenomas associated with FAP (11,12). 'Two-hit ' inactivation of the APC gene also occurs in sporadic gastrointestinal epithelial tumors (13,14). In spite of the different histogenetic derivation, recent evidence suggests that inactivation of both alleles of the APC gene plays a rol