• What is PIK3CA?
  • PIK3CA in Colorectal Cancer
  • Clinical Trials


Phosphatidyl 3-kinases (PI3K) are a family of lipid kinases involved in many cellular processes, including cell growth, proliferation, differentiation, motility, and survival. PI3K is a heterodimer composed of 2 subunits—an 85 kDa regulatory subunit (p85) and a 110 kDa catalytic subunit. The PIK3CA gene encodes p110α, one of the catalytic subunits.

PI3K converts PI(4,5)P2 [Phosphatidylinositol 4,5-bisphosphate] to PI(3,4,5)P3 [Phosphatidylinositol (3,4,5)-trisphosphate] on the inner leaflet of the cell membrane. PI(3,4,5)P3 recruits important downstream signaling proteins, such as AKT, to the cell membrane resulting in increased activity of these proteins.

Mutant PIK3CA has been implicated in the pathogenesis of several cancers, including colon cancer, gliomas, gastric cancer, breast cancer, endometrial cancer, and lung cancer (COSMICSamuels et al. 2004)



Figure 1.
Schematic of the MAPK and PI3K pathways. . Growth factor binding to receptor tyrosine kinase results in activation of the MAPK signaling pathway (RAS-RAF-MEK-ERK) and the PI3K pathway (PI3K-AKT-mTOR). The letter "K" within the schema denotes the tyrosine kinase domain.

Related Pathways

Contributors: Leora Horn, M.D., M.Sc., William Pao, M.D., Ph.D. (through April 2014), Christine M. Lovly, M.D., Ph.D.

Suggested Citation: Horn, L., W. Pao, C. Lovly. 2015. PIK3CA. My Cancer Genome https://www.padiracinnovation.org/content/disease/colorectal-cancer/pik3ca/?tab=0 (Updated December 7).

Last Updated: December 7, 2015

PIK3CA in Colorectal Cancer

Somatic mutations in PIK3CA have been found in 10–30% of colorectal cancers (COSMICSamuels et al. 2004).

These mutations usually occur within two "hotspot" areas within exon 9 (the helical domain) and exon 20 (the kinase domain).

Gene Exon Location Amino Acid Position Amino Acid Change Nucleotide Change Frequency Among PIK3CA-Mutated Colon Cancer (COSMIC)
PIK3CA 9 Helical domain E542 p.E542K c.1624G>A 17%
E545 p.E545K c.1633G>A 28%
p.E545Q c.1633G>C 0.3%
p.E545G c.1634A>G 2.1%
p.E545V c.1634A>T 0.2%
Q546 p.Q546K c.1636C>A 4.2%
p.Q546E c.1636C>G 0.3%
p.Q546P c.1637A>C 0.2%
p.Q546R c.1637A>G 0.5%
p.Q546L c.1637A>T 0.3%​
D549 p.D549N c.1645G>A 0.4%
20 Kinase Domain H1047 p.H​1047R c.3140A>G 21%
p.H1047L c.3140A>T 4.0%


Contributors: Alberto Bardelli, Ph.D.

Suggested Citation: Bardelli, A. 2015. PIK3CA in Colorectal Cancer. My Cancer Genome https://www.padiracinnovation.org/content/disease/colorectal-cancer/pik3ca/ (Updated August 28).

Last Updated: August 28, 2015

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