Somatic mutations in CTNNB1 (Beta-catenin) have been found in ~2-3% of malignant melanomas. Preclinical models have demonstrated that concurrent mutations in Beta-catenin and NRAS are synergistic in promoting melanoma formation.

Mutations in beta catenin (CTNNB1) are seen in about 90% of adamantinomatous craniopharyngiomas and mutations in BRAF (V600E) in papillary craniopharyngiomas. Adamantinomatous and papillary craniopharyngiomas have been shown to carry clonal mutations that are mutually exclusive. These findings indicate that the adamantinomatous and papillary subtypes have distinct molecular underpinnings, each principally driven by mutations in a single well-established oncogene - CTNNB1 in the adamantinomatous form and BRAF in the papillary form, independent of age. This may have implications for the diagnosis and treatment of these tumors.

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. Mutations in exon 3 of CTNNB1 result in stabilization of a protein that resists degradation, leading to nuclear accumulation of b-catenin, have been described in endometrioid endometrial carcinoma. The reported frequency of CTNNB1 mutations in endometrioid endometrial carcinoma ranges from 14-44%. However, these mutations are not described previously in endometrial sarcomas. Of note, CTNNB1 mutations are highly common in desmoid fibromatosis.

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.