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Interpretation 2144
Tier 2
APC
Variants
APC I1307K
Primary Sites
Colon
Rectum
Tumor Types
Adenocarcinoma
Interpretation

Somatic APC mutations are common events in colorectal adenocarcinomas, reported in up to 76% of the cases. Loss of normal APC function is known to be an early event in both familial and sporadic colon cancer pathogenesis, occurring at the pre-adenoma stage. APC mutations do not appear to significantly affect the prognosis of colorectal cancer patients. While there are a number of small molecule inhibitors in development that target the Wnt pathway, there is currently no matched targeted therapy available for colorectal cancer patients harboring an APC mutation. 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. 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. Correlation with other clinical and lab findings is recommended.

Citations
  1. Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012;487(7407):330-7
  2. Han SW, et al. Targeted sequencing of cancer-related genes in colorectal cancer using next-generation sequencing. PLoS One 2013;8(5):e64271
  3. Prall F, et al. Phenotypes of invasion in sporadic colorectal carcinomas related to aberrations of the adenomatous polyposis coli (APC ) gene. Histopathology 2007;50(3):318-30
  4. Kim JT, et al. Deregulation of Wnt/b-catenin signaling through genetic or epigenetic alterations in human neuroendocrine tumors. Carcinogenesis 2013;34(5):953-61
  5. Vasovcak P, et al. Molecular genetic analysis of 103 sporadic colorectal tumours in Czech patients. PLoS One 2011;6(8):e24114
  6. 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
  7. 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: 2018-03-16 19:52:48 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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