Oncogenic mutations of the PIK3CA gene in head and neck squamous cell carcinomas

  • Authors:
    • Avaniyapuram Kannan Murugan
    • Nguyen Thi Hong
    • Yasuhisa Fukui
    • Arasambattu Kannan Munirajan
    • Nobuo Tsuchida
  • View Affiliations

  • Published online on: January 1, 2008     https://doi.org/10.3892/ijo.32.1.101
  • Pages: 101-111
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Phosphatidylinositol 3-kinases (PI3Ks) are heterodimeric lipid kinases that regulate cellular activities such as proliferation, survival, motility and morphology. Recent studies reported that the p110α (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.

Related Articles

Journal Cover

January 2008
Volume 32 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Murugan AK, Hong NT, Fukui Y, Munirajan AK and Tsuchida N: Oncogenic mutations of the PIK3CA gene in head and neck squamous cell carcinomas. Int J Oncol 32: 101-111, 2008.
APA
Murugan, A.K., Hong, N.T., Fukui, Y., Munirajan, A.K., & Tsuchida, N. (2008). Oncogenic mutations of the PIK3CA gene in head and neck squamous cell carcinomas. International Journal of Oncology, 32, 101-111. https://doi.org/10.3892/ijo.32.1.101
MLA
Murugan, A. K., Hong, N. T., Fukui, Y., Munirajan, A. K., Tsuchida, N."Oncogenic mutations of the PIK3CA gene in head and neck squamous cell carcinomas". International Journal of Oncology 32.1 (2008): 101-111.
Chicago
Murugan, A. K., Hong, N. T., Fukui, Y., Munirajan, A. K., Tsuchida, N."Oncogenic mutations of the PIK3CA gene in head and neck squamous cell carcinomas". International Journal of Oncology 32, no. 1 (2008): 101-111. https://doi.org/10.3892/ijo.32.1.101