Novel somatic mutations of <i>PIK3CA</i> in patients with colorectal cancer

Colorectal cancer (CRC) is a heterogenous disease with varying genetic and epigenetic backgrounds. The phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit alpha (<em>PIK3CA</em>) gene encodes for the catalytic subunit p110&alpha; of phosphatidylinositol 3‑kinase (PI3K). Determining the frequency of <em>PIK3CA</em> mutations in CRC in different populations may enhance the current understanding of the pathogenicity of CRC and may aid in the prognosis of affected patients. The present study included 71 male and female patients with clinically confirmed CRC (58 colon cancer cases and 13 rectal cancer cases). Mutations in exon 9 and 20 of the <em>PIK3CA</em> gene were identified using Sanger capillary sequencing. A total of 6 patients carried mutations in either exon 9 or 20 of the <em>PIK3CA</em> gene. The majority of the colon tumors (83.3%) with the <em>PIK3CA</em> mutation presented at an advanced stage of the disease and the mutations were found more frequently among women (66.6%). All missense mutations (E545A and L1001V) and novel mutations (two) were only observed in the samples from female patients. The two novel <em>PIK3CA</em> gene mutations that were identified in the present study are a missense mutation leading to a c.3001C&gt;G, p.L1001V amino acid change and a nonsense mutation c.3153 G&gt;A, W1051Ter leading to protein termination in exon 20. The patients with these mutations presented with a poor prognosis. The novel mutations identified in the kinase domain of PIK3CA may induce the hyperactivation of the protein in the PI3K pathway, leading to a poor prognosis. CRC screening is recommended at an early age (&gt;40 years) for all patients, but particularly for females who carry these mutations.