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Interpretation 370
Tier 3
APC
Variants
APC I1307K
Primary Sites
Pancreas
Tumor Types
Adenocarcinoma
Interpretation

The APC gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. APC promotes rapid degradation of beta-catenin and participates in Wnt signaling as a negative regulator. APC is also involved in other processes including cell migration, cell adhesion, transcriptional activation and apoptosis. Germline defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Disease-associated mutations tend to be clustered in a small region designated the mutation cluster region (MCR) and result in a truncated protein product. Pancreatic cancer is considered a low risk cancer, though it is observed in FAP families with higher incidence than the general populations. Somatic APC mutations have been reported in ~1% of pancreatic ductal adenocarcinomas (PDAC). Codon I1307 lies within a regulatory region of the APC protein mediated by ubiquitination. APC I1307K is associated with increased colorectal cancer risk by making the gene unstable and prone to acquire mutations during normal cell division. The germline APC I1307K gene mutation is most commonly found in people of Ashkenazi Jewish descent. Therefore, routine colorectal screening is very important in these individuals. The prognostic and therapeutic implications of APC mutations in PDAC remain to be fully elucidated. Correlation with other clinical and lab findings is recommended.

Citations
  1. Boman BM, et al. An APC:WNT Counter-Current-Like Mechanism Regulates Cell Division Along the Human Colonic Crypt Axis: A Mechanism That Explains How APC Mutations Induce Proliferative Abnormalities That Drive Colon Cancer Development. Front Oncol 2013;3():244
  2. Solomon S, et al. Inherited pancreatic cancer syndromes. Cancer J 2012;18(6):485-91
  3. Witkiewicz AK, et al. Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets. Nat Commun 2015;6():6744
  4. Bailey P, et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 2016;531(7592):47-52
  5. Frayling IM, et al. The APC variants I1307K and E1317Q are associated with colorectal tumors, but not always with a family history. Proc Natl Acad Sci U S A 1998;95(18):10722-7
  6. Zauber P, et al. Colorectal tumors from APC*I1307K carriers principally harbor somatic APC mutations outside the A8 tract. PLoS One 2014;9(1):e84498
Last updated: 2017-01-30 21:57:13 UTC
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