Phosphatidylinositol 3-kinases (PI3Ks) are heterodimeric
lipid kinases that regulate cellular activities such as proliferation, survival, motility and morphology. Recent studies reported that the p110alpha (PIK3CA), catalytic subunit of
PI3-kinase is somatically mutated in human
cancers. Hot- spot mutations (E542K, E545K and H1047R) are reported to have higher oncogenic potential. Although PIK3CA mutations were reported in
head and neck squamous cell carcinomas (
HNSCC) of limited ethnicity, the functional consequences of
HNSCC-associated PIK3CA mutations have not been examined. Status of PI3K signaling related genes (PTEN-RAS-EGFR) in the presence of PIK3CA mutation have not been reported. In this study, we analyzed exons 9 and 20 of PIK3CA in 54 samples, including 17
HNSCC cell lines, 19 Indian and 18 Vietnamese primary
tumors. We found mutations in 29.4% (5/17) of
HNSCC cell lines, 10.5% (2/19) of Indian
tumors and no mutation (0/18) in Vietnamese
tumors. Two homozygous PIK3CA mutations were found in cell lines and a novel insertion mutation with oncogenicity in Indian
tumor. Analysis of PI3K signaling related genes showed that PIK3CA and PTEN mutations were mutually exclusive, though PTEN mutation is uncommon in
HNSCC. However, PIK3CA mutation coexisted with H-RAS mutation. Furthermore, PIK3CA mutations were mutually exclusive to EGFR amplification. All the 5 mutants that we found in
HNSCC, showed increased
PI3 kinase activities, followed by
growth factor independent higher colony forming efficiency, changes in morphology, higher rates of migration and invasion compared with PIK3CA wild-type. Our study is the first to examine the oncogenic potential of PIK3CA mutants associated with
HNSCC and report on PIK3CA mutations in Indian and Vietnamese ethnicity. These results suggest that PIK3CA mutations in
HNSCC are likely to be oncogenic and may significantly contribute to
HNSCC carcinogenesis and pave attractive target for therapeutic prevention.