Association of PIK3CA gene mutations with head and neck squamous cell carcinomas.

UNLABELLED: The Phosphoinositide-3-kinase catalytic alpha polypeptide (PIK3CA) is an important regulator of cell signaling pathways in human cancers. Mutations in PIK3CA were found to be associated with more aggressive clinical outcome and aberrant activation of cellular mechanisms in cancers. Hence the present study aimed to understand the mutations in the PIK3CA gene in head and neck squamous cell carcinomas (HNSCC). After the approval of the Institutional Ethics Committee we recruited 129 HNSCC patients and 150 healthy controls for screening of mutations in the helical (exon9) and kinase domain (exon 20) of the PIK3CA gene using PCR, SSCP and Sanger Sequencing. We found about 60.46% of HNSCC patients and 26% of controls with the following mutations 1634A>C (E545A) and 3075C>T (T1025T) in the helical and kinase domains of PIK3CA. Both these mutations 1634A>C and 3075C>T were more prominent in oral cancers, advanced stages of HNSCC and tobacco plus alcohol habits (p<0.05). Hence, we conclude that the distribution of mutations of PIK3CA in HNSCC were associated with demographic (tobacco and alcohol) and clinical parameters (advanced stage, primary site) of HNSCC. It is possible that when this pathway is overactive due to mutations, it may reduce apoptosis and allow proliferation of the tumor cells. Therefore we propose that these mutations may serve as prognostic biomarkers, and can also be proposed as novel therapeutic targets for HNSCC. KEYWORDS: PI3 kinase, gene polymorphism, helical domain, kinase domain, oral cancers.