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 appear to be more common in squamous cell histology compared to adenocarcinoma and can occur with or without a history of smoking. PIK3CA mutations can co-occur with EGFR mutations and PIK3CA mutations have been detected in a small percentage (approximately 5%) of EGFR-mutated lung cancers with acquired resistance to EGFR TKI therapy. The PIK3CA H1047R mutation is known to be oncogenic.
Gymnopoulos M, Elsliger MA, Vogt PK. Rare cancer-specific mutations in PIK3CA
show gain of function. Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5569-74. Epub 2007 Mar 21.
Bader AG, Kang S, Zhao L, Vogt PK. Oncogenic PI3K deregulates transcription
and translation. Nat Rev Cancer. 2005 Dec;5(12):921-9. Review.
Sequist L et al.. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med. 2011 Mar 23;3(75):75ra26.
Kawano O, et al. PIK3CA mutation status in Japanese lung cancer patients. Lung Cancer 2006;54(2):209-15.
Cancer Genome Atlas Research Network. Comprehensive molecular profiling of
lung adenocarcinoma. Nature. 2014 Jul 31;511(7511):543-50.
Comprehensive TCGA PanCanAtlas (https://gdc.cancer.gov/about-data/publications/pancanatlas).
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