These findings demonstrate (i) that FAP and FIF are allelic, and (ii) that APC gene mutations which truncate the APC protein distal to the beta-catenin binding domain are associated with desmoid tumours, absent CHRPE and variable but attenuated polyposis expression.
The demonstration of mutations in two mediators in the Wnt-APC-beta-catenin pathway implicates beta-catenin stabilization as the key factor in the pathogenesis of aggressive fibromatosis.
To investigate whether this hypothesis could be extended to other Wnt-dependent tumor types, we searched for WT1 mutations and studied WT1 expression in beta-catenin mutant desmoid tumors.
FAP results from germline adenomatous polyposis coli (APC) gene mutations and desmoids arise following biallelic APC mutation, with one change usually occurring distal to the second beta-catenin binding/degradation repeat of the gene (3' to codon 1399).
Accumulation of altered beta-catenin associated with a somatic heterozygous activating mutation in codon 41 was detected in the typical desmoid-type fibromatosis and at the ossifying focus.
The aim of this study is to investigate the immunohistochemical profile and the involvement of the beta-catenin pathway in desmoplastic fibroma as it is known in desmoid-type fibromatosis.
While tumours from the colorectum and upper gastrointestinal tract usually retain one to two and three to four beta-catenin degradation repeats, respectively, most desmoids preferentially retain two repeats (P < 0.001, chi2 test).
SAMD9 is expressed at a lower level in a variety of neoplasms associated with beta-catenin stabilization, such as aggressive fibromatosis, breast, and colon cancers.