CTNNB1 mutations are highly prevalent and were detected in 84 to 87% of all sporadic fibromatosis/desmoid tumors. Most CTNNB1 mutations in fibromatosis/desmoid tumors are predominantly missense mutations in codons 41 and 45 of exon 3. These mutations result in β-catenin stabilization, increased nuclear accumulation and activation of the Wnt signaling pathway. Specific CTNNB1 mutations have been reported to predict recurrence in some cases of extra-abdominal and abdominal aggressive fibromatosis. A S45F mutation increased the risk of recurrence significantly.

Beta catenin is a transcriptional co-regulator and an adapter protein for cellular adhesion; it comprises part of the Wnt signaling pathway and intracellular levels of beta-catenin are regulated by its phosphorylation, ubiquitination and proteosomal degradation. Accumulation of nuclear beta catenin can lead to a tumoral phenotype and oncogenic transformation in a variety of solid tumors. Various oncogenic mutants of beta catenin have been found in different tumor types which alter its degradation, leading to its accumulation and promoting tumor growth. CTNNB1 mutations are particularly common in colorectal carcinomas associated with hereditary non-polyposis colon cancer syndrome and wild type APC gene, and are extremely rare in sporadic colorectal cancers. These mutations consist almost entirely of transitions at codons 41 and 45, and result in stabilization of a protein that resists degradation, leading to nuclear accumulation of β-catenin. Up to 50% of primary colorectal carcinomas with CTNNB1 mutations exhibit microsatellite instability, suggesting that CTNNB1 mutations may be more common in the DNA mismatch repair pathway of tumorigenesis. Microsatellite instability is generally associated with better prognosis when compared to patients with intact mismatch repair pathways. Preclinical studies suggest that CTNNB1 mutations may confer resistance to PI3K-AKT inhibitors in colorectal cancer.

Beta catenin is a transcriptional co-regulator and an adapter protein for cellular adhesion; it comprises part of the Wnt signaling pathway and intracellular levels of beta-catenin are regulated by its phosphorylation, ubiquitination and proteosomal degradation. Accumulation of nuclear beta catenin can lead to a tumoral phenotype and oncogenic transformation in a variety of solid tumors. Various oncogenic mutants of beta catenin have been found in different tumor types which alter its degradation, leading to its accumulation and promoting tumor growth. Some of these mutations are located at the N-terminus of the protein at the sites of phosphorylation which normally regulate its degradation. Interestingly, in a recent study, 38% of patients with myelodysplastic syndromes or acute myeloid leukaemia, showed increased β-catenin signalling and nuclear accumulation of beta catenin in osteoblasts was associated with increased Notch signalling in haematopoietic cells consistent with a model where abnormalities of osteolineage cells are associated with myeloid malignancies. In addition, aberrant Wnt siganling has been reported to play a role in chronic myeloid leukemia, acute lymphoblastic leukemia and non-hodgkin lymphomas. Inhibition of beta catenin using small molecule inhibitors is currently being investigated in various tumor types. Recent studies suggest that targeting of the Wnt pathway and beta catenin may be promising targets in the therapy of acute myeloid leukemia.