|Variant(s)||CTNNB1 codon(s) 41, 45 any|
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.
Mirabelli-Primdahl L, et al. Beta-catenin mutations are specific for colorectal carcinomas with microsatellite instability but occur in endometrial carcinomas irrespective of mutator pathway. Cancer Res 1999;59(14):3346-51
Kim IJ, et al. Development and applications of a beta-catenin oligonucleotide microarray: beta-catenin mutations are dominantly found in the proximal colon cancers with microsatellite instability. Clin Cancer Res 2003;9(8):2920-5
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