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402949 | New Interpretation | 01/22/2019 1:49 PM |
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Tier 2InterpretationCTNNB1 encodes b-catenin, a transcriptional co-regulator and an adapter protein for cellular adhesion involved in the WNT signaling pathway. Somatic gain-of-function mutations in CTNNB1 result in aberrant accumulation of the b-catenin protein and are prevalent in a wide range of solid tumors, including uterine/endometrial carcinoma, ovarian, hepatocellular carcinoma, and colorectal carcinoma, among others. 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. CTNNB1 is altered in 2.9% of pancreatic adenocarcinomas. The CTNNB1 T41A mutation is known to be oncogenic. Preclinical studies suggest that CTNNB1 mutations may confer resistance to PI3K-AKT inhibitors in colorectal cancer. Cancers with CTNNB1 mutations are presumed to be resistant to pharmacologic inhibition of upstream components of the WNT pathway, instead requiring direct inhibition of b-catenin function. The role of CTNNB1 mutations in pancreatic adenocarcinomas requires further elucidation.
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- Tenbaum SP, et al. b-catenin confers resistance to PI3K and AKT inhibitors and subverts FOXO3a to promote metastasis in colon cancer. Nat Med 2012;18(6):892-901
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- Comprehensive TCGA PanCanAtlas (https://gdc.cancer.gov/about-data/publications/pancanatlas)
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Last updated: 2019-01-22 18:49:51 UTC
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