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CTNNB1
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Interpretation 2317
Tier 2
CTNNB1
Variants
CTNNB1 T41A
Primary Sites
Ampulla (Pancreaticobiliary Duct)
Tumor Types
Adenocarcinoma
Interpretation

CTNNB1 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.

Citations
  1. 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
  2. Bougatef K, et al. Prevalence of mutations in APC, CTNNB1, and BRAF in Tunisian patients with sporadic colorectal cancer. Cancer Genet Cytogenet 2008;187(1):12-8
  3. Clevers H, Nusse R. Wnt/b-catenin signaling and disease. Cell. 2012 Jun 8;149(6):1192-205. doi: 10.1016/j.cell.2012.05.012. Review.
  4. Garber K. Drugging the Wnt pathway: problems and progress. J Natl Cancer Inst. 2009 Apr 15;101(8):548-50.
  5. Fukuchi T, Sakamoto M, Tsuda H, Maruyama K, Nozawa S, Hirohashi S. Beta-catenin mutation in carcinoma of the uterine endometrium. Cancer Res. 1998 Aug 15;58(16):3526-8.
  6. Valenta T, Hausmann G, Basler K. The many faces and functions of b-catenin. EMBO J. 2012 Jun 13;31(12):2714-36. doi: 10.1038/emboj.2012.150. Epub 2012 May 22. Review
  7. 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
  8. 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
  9. Popat S, et al. Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol 2005;23(3):609-18
  10. Comprehensive TCGA PanCanAtlas (https://gdc.cancer.gov/about-data/publications/pancanatlas)
Last updated: 2019-01-22 18:49:51 UTC
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