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CTNNB1
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Interpretation 15
Tier 1
CTNNB1
Variants
CTNNB1 codon(s) 32, 33, 34, 35, 36, 37, 41, 45 any
CTNNB1 S45P
CTNNB1 G34E
CTNNB1 S37C
CTNNB1 S37F
CTNNB1 D32V
CTNNB1 codon(s) 41, 45 any
CTNNB1 S37Y
Primary Sites
Blood
Bone Marrow
Tumor Types
Myelodysplastic Syndrome
Acute Myeloid Leukemia
Interpretation

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.

Citations
  1. Thakur R, et al. Pharmacological modulation of beta-catenin and its applications in cancer therapy. J Cell Mol Med 2013;17(4):449-56
  2. Kode A, et al. Leukaemogenesis induced by an activating b-catenin mutation in osteoblasts. Nature 2014;506(7487):240-4
  3. Wang L, et al. b-Catenin and AKT are promising targets for combination therapy in acute myeloid leukemia. Leuk Res 2013;37(10):1329-40
  4. Sercan Z, et al. Beta-catenin mutations are not observed in chronic myeloid leukemia. Tumori 2009;95(6):836-9
  5. Groen RW, et al. Illegitimate WNT pathway activation by beta-catenin mutation or autocrine stimulation in T-cell malignancies. Cancer Res 2008;68(17):6969-77
  6. Hoshida Y, et al. Analysis of p53, K-ras, c-kit, and beta-catenin gene mutations in sinonasal NK/T cell lymphoma in northeast district of China. Cancer Sci 2003;94(3):297-301
Last updated: 2016-06-04 21:23:20 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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