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PIK3CA
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Interpretation 307
Tier 2
PIK3CA
Variants
PIK3CA E542K
PIK3CA E545K
PIK3CA H1047R
PIK3CA codon(s) 542, 545, 1047 any
Primary Sites
Anus
Oral Cavity
Pharynx
Lung
Tumor Types
Squamous Cell Carcinoma
Interpretation

The catalytic subunit (p110a) of phosphatidylinositol-3-kinase (PI3K) is encoded by the PIK3CA gene and acts to activate several signaling cascades, including the well-characterized AKT-mTOR pathway that promotes cell survival, proliferation, growth and motility. PIK3CA is among the most commonly mutated genes in cancer and aberrant activation of PI3K is a transforming event. Somatic mutations in PIK3CA have been found in 1--3% of NSCLC and genetic alteration in PIK3CA have been identified in 7% of lung adenocarcinomas. These mutations typically occur within specific hotspot regions. PIK3CA mutations activate the PI3K-PTEN-AKT pathway which is downstream from both the EGFR and the RAS-RAF-MAPK pathways. The somatic mutations found thus far in PIK3CA are oncogenic, and the majority of them are clustered within exon 9 and 20 (helical and kinase domains), with three hotspots (E542K, E545K, and H1047R/L). PIK3CA mutations have been reported in 8-21% and 20-33% of head/neck and anal squamous cell carcinoma, respectively. PIK3CA mutations, especially ones involving the helical domain, in these types of squamous cell carcinoma are highly associated with HPV. The predictive and prognostic significance of PIK3CA mutations in squamous cell carcinoma is unclear and needs further elucidation. Clinical trials targeting PI3K/Akt/mTor pathway inhibitors are available for patients with PIK3CA mutated tumors.

Citations
  1. Stransky N, et al. The mutational landscape of head and neck squamous cell carcinoma. Science 2011;333(6046):1157-60
  2. Cancer Genome Atlas Network Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 2015;517(7536):576-82
  3. Cacheux W, et al. Mutational analysis of anal cancers demonstrates frequent PIK3CA mutations associated with poor outcome after salvage abdominoperineal resection. Br J Cancer 2016;114(12):1387-94
  4. Smaglo BG, et al. Comprehensive multiplatform biomarker analysis of 199 anal squamous cell carcinomas. Oncotarget 2015;6(41):43594-604
  5. Zhang P, et al. Molecular heterogeneity of head and neck squamous cell carcinoma defined by next-generation sequencing. Am J Pathol 2014;184(5):1323-30
Last updated: 2019-03-11 16:30:45 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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