DOI QR코드

DOI QR Code

Mutations in the tyrosine kinase domain of the EGFR gene are rare in the Korean Oral Squamous Cell Carcinoma

  • Lee, Eun-Ju (Dept. of Clinical Laboratory Science, Daejeon Health Institute of technology)
  • Received : 2016.08.09
  • Accepted : 2016.09.20
  • Published : 2016.09.30

Abstract

The epidermal growth factor receptor(EGFR) protein kinase signaling is an important pathway in cancer development and recently reported that EGFR and its kinase domain molecules are mutated in various of cancers including head and neck cancer. Functional deregulation of EGFR due to mutations in coding exons and copy number amplification is the most common event in cancers, especially among receptor tyrosine kinases(TK). We have analyzed Korean oral squamous cell carcinomas (OSCC) cell lines for mutations in EGFRTK. Exons encoding the hot-spot regions in the TK domain of EGFR (exons 17 to 23) were amplified by using polymerase chain reaction(PCR) and sequenced directly. EGFR expression was also analyzed in 8 OSCC cell lines using western blotting. Data analysis of the EGFR exons 17 to 23 coding sequences did not show any mutations in the 8 OSCC cell lines that were analyzed. The absence of mutations indicate that protein overexpression might be responsible for activation rather than mutation.

Keywords

References

  1. Milas, K. A. Mason, Z. Liao, K. K. Ang, "Chemoradiotherapy: emerging treatment improve ment strategies", Head Neck, vol. 25, pp. 152-67, 2003. https://doi.org/10.1002/hed.10232
  2. C. J. Langer, "Exploring Biomarkers in Head and Neck Cancer" Cancer, vol 118, No. 16, pp. 3882-3892, Jan, 2012 https://doi.org/10.1002/cncr.26718
  3. E.S. Lampri, G. Chondrogiannis, E. loachim et al., "Biomarkers of head and neck cancer, tools or a gordian knot?", Int J Clin Exp Med, Vol. 8, No. 7, pp. 10340-10357, 2015
  4. S. P. D'Angelo, M. C. Pietanza, M. L. Johnson et al "Incidence of EGFR exon 19 deletions and L858R in tumor specimens from men and cigarette smokers with lung adenocarcinomas" J Clin Oncol, vol. 29, pp. 2066-2070, 2011. https://doi.org/10.1200/JCO.2010.32.6181
  5. A. F. Gazdar, "Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors", Oncogene, vol. 28, pp. 24-31, 2009. https://doi.org/10.1038/onc.2009.198
  6. F. Ciardiello and G. Tortora "A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor", Clin Cancer Res, vol. 7. pp. 2958-2970, 2001.
  7. Q. Liu, G. Ma, H. Yang et al, "Lack of epidermal growth factor receptor gene mutations in exons 19 and 21 in primary lymphoepithelioma-like carcinoma of the lung", Thoracic Cancer, vol. 5, pp. 63-67, 2013.
  8. P. Stephens, C. Hunter, G. Bignell et al., "Lung cancer: intragenic ERBB2 kinase mutations in tumors", Nature, vol. 431, pp. 525-526, 2004.
  9. H. Shigematsu, L. Lin, T. Takahashi et al., "Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers", J Natl Cancer Inst, vol. 97, pp. 339-462, 2005. https://doi.org/10.1093/jnci/dji055
  10. E. J. Lee, J. Kim, S. A. Lee, E. J. Kim, Y. C. Chun, M. H. Ryu, J. I. Yook, "Characterization of newly established oral cancer cell lines derived from six squamous cell carcinoma and two muco epidermoid carcinoma cells", Exp Mol Med., vol. 37, pp. 379-390, 2005. https://doi.org/10.1038/emm.2005.48
  11. N. K. Jeon, J. Kim, E. J. Lee, "The GSK-$3{\beta}$/Cyclin D1 Pathway is Involved in the Resistance of Oral Cancer Cells to the EGFR Tyrosine Kinase Inhibitor ZD1839", Bio Sci Letters, vol. 20, No. 2, pp. 85-95, 2014.
  12. S. Rajendran, R. S. Muthupalani, A. Ramanathan, "Lack of RING finger domain (RFD) mutations of the c-cbl gene in oral squamous cell carcinomas in Chennai, India", Asian Pac J Cancer Prev, vol. 14, pp. 1073-1075, 2013. https://doi.org/10.7314/APJCP.2013.14.2.1073
  13. E. E. Cohen, F. Rosen, and W. M. Stadler et al. "Phase II trial of ZD1839 in recurrent or metastatic squamous cell carcinoma of the head and neck", J Clin Oncol vol. 21, pp. 1980-1987, 2003. https://doi.org/10.1200/JCO.2003.10.051
  14. P. M. Harari, S. M. Huang, R. S. Herbst and H. Quon, "Molecular Targeting of the Epidermal Growth Factor Receptor. In: Harrison LB, Session RB, Hong WK, editors. Head and Neck Cancer" A Multidisciplinary Approach. 2nded. Philadelphia: Lippincott, Williams and Wilkings, 2003.
  15. T. Fukui, T. Mitsudomi, "Gefitinib and epidermal growth factor receptor gene mutation", Gan Kagaku Ryoho vol.34, pp.1168-1172, 2007.
  16. A. F. Gazdar, H. Shigematsu, J. Herz, J. D. Minna, "Mutations and addiction to EGFR: the Achilles heal of lung cancers?", Trends Mol Med, vol.10, pp.481-486, 2004. https://doi.org/10.1016/j.molmed.2004.08.008
  17. E. E. Cohen, M. W. Lingen, L. E. Martin et al. "Response of some head and neck cancers to epidermal growth factor receptor tyrosine kinase inhibitors may be linked to mutation of ERBB2 rather than EGFR", Clin Cancer Res, vol.11, pp. 8105-8108, 2005. https://doi.org/10.1158/1078-0432.CCR-05-0926
  18. S. E. Wang, A. Narasanna, M. Perez-Torres et al., "HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors", Cancer Cell, vol. 10, pp. 25-38, 2006. https://doi.org/10.1016/j.ccr.2006.05.023
  19. Y. Lemos-Gonzalez, M. Paez de la Cadena, F. J. Rodriguez-Berrocal, A. M. Rodriguez-Pineiro, E. Pallas, D. Valverde, "Absence of activating mutations in the EGFR kinase domain in Spanish head and neck cancer patients" Tumour Biol, vol. 28, pp. 273-279, 2007. https://doi.org/10.1159/000110425
  20. J. Loeffler-Ragg, M. Witsch-Baumgartner, A. Tzankov et al., "Low incidence of mutations in EGFR kinase domain in Caucasian patients with head and neck squamous cell carcinoma", Eur J Cancer, vol. 42, pp. 109-111, 2006. https://doi.org/10.1016/j.ejca.2005.08.034
  21. J. W. Lee, Y. H Soung, S. Y. Kim et al., "Absence of EGFR mutation in the kinase domain in common human cancers besides non-small cell lung cancer", Int J Cancer, vol. 113, pp. 510-511, 2006.