Cancer Chemotherapy and Pharmacology

, Volume 58, Supplement 1, pp 39–41 | Cite as

EGFR mutation in various tissues

  • Kazuto NishioEmail author
  • Tokuzo Arao
  • Terufumi Kato
  • Hideyuki Yokote


Somatic mutations have been demonstrated in various tumors. EGFR mutations were first demonstrated in adenocarcinoma of the lung, and a large-scale retrospective study has clearly shown that these mutations are specifically observed in this form of the disease. Recently, possible occurrence of EGFR mutations in other tumor types including ovarian and colorectal malignancies has been reported. This raises the possibility of application of EGFR-specific tyrosine kinase inhibitors (EGFR-TKI) to the treatment of these malignancies, although broad success in this venture would depend on the frequency of such mutations. In this article, we discuss somatic mutations in various tumors as well as potential application of TKI to their treatment. Ethnic difference in the frequency of somatic mutations is another area of interest since it is closely related to clinical response to EGFR-TKIs. Preliminary studies have revealed such ethnic variations regarding EGFR mutation and gene amplification. Ethnic difference of transcriptional regulation of EGFR has also been demonstrated. We recently found a biomarker related to clinical response to EGFR-TKI that might explain the ethnic differences in response to this therapy. Various tyrosine kinases are known targets of TKIs. Thus genomics of individual patients may allow personalized target-based therapeutics.


EGFR mutation Tyrosine kinase inhibitor Ethnicity HLA 



We thank Dr. N. Thatcher (Christie Hosp NHS Trust) for personal communication with T. Kato.


  1. 1.
    Amador ML, Oppenheimer D, Perea S, Maitra A, Cusati G, Iacobuzio-Donahue C, Baker SD, Ashfaq R, Takimoto C, Forastiere A, Hidalgo M (2004) An epidermal growth factor receptor intron 1 polymorphism mediates response to epidermal growth factor receptor inhibitors. Cancer Res 64:9139–9143PubMedCrossRefGoogle Scholar
  2. 2.
    Calvo E, Baselga J (2006) Ethnic differences in response to epidermal growth factor receptor tyrosine kinase inhibitors. J Clin Oncol 24:2158–2163PubMedCrossRefGoogle Scholar
  3. 3.
    Cohen EE, Lingen MW, Martin LE, Harris PL, Brannigan BW, Haserlat SM, Okimoto RA, Sgroi DC, Dahiya S, Muir B, Clark JR, Rocco JW, Vokes EE, Haber DA, Bell DW (2005) 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 11:8105–8108PubMedCrossRefGoogle Scholar
  4. 4.
    Douglas DA, Zhong H, Ro JY, Oddoux C, Berger AD, Pincus MR, Satagopan JM, Gerald WL, Scher HI, Lee P, Osman I (2006) Novel mutations of epidermal growth factor receptor in localized prostate cancer. Front Biosci 11:2518–2525PubMedCrossRefGoogle Scholar
  5. 5.
    Gwak GY, Yoon JH, Shin CM, Ahn YJ, Chung JK, Kim YA, Kim TY, Lee HS (2005) Detection of response-predicting mutations in the kinase domain of the epidermal growth factor receptor gene in cholangiocarcinomas. J Cancer Res Clin Oncol 131:649–652PubMedCrossRefGoogle Scholar
  6. 6.
    Klein B, Klein T, Nyska A, Shapira J, Figer A, Schwartz A, Rakovsky E, Livni E, Lurie H (1991) Expression of HLA class I and class II in gastric carcinoma in relation to pathologic stage. Tumour Biol 12:68–74PubMedGoogle Scholar
  7. 7.
    Lee JW, Soung YH, Kim SY, Nam HK, Park WS, Nam SW, Kim MS, Sun DI, Lee YS, Jang JJ, Lee JY, Yoo NJ, Lee SH (2005) Somatic mutations of EGFR gene in squamous cell carcinoma of the head and neck. Clin Cancer Res 11:2879–2882PubMedCrossRefGoogle Scholar
  8. 8.
    Lee SC, Lim SG, Soo R, Hsieh WS, Guo JY, Putti T, Tao Q, Soong R, Goh BC (2006) Lack of somatic mutations in EGFR tyrosine kinase domain in hepatocellular and nasopharyngeal carcinoma. Pharmacogenet Genomics 16:73–74PubMedCrossRefGoogle Scholar
  9. 9.
    Liu W, Innocenti F, Chen P, Das S, Cook EH Jr, Ratain MJ (2003) Interethnic difference in the allelic distribution of human epidermal growth factor receptor intron 1 polymorphism. Clin Cancer Res 9:1009–1012PubMedGoogle Scholar
  10. 10.
    Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350:2129–2139PubMedCrossRefGoogle Scholar
  11. 11.
    Ogoshi K, Tajima T, Mitomi T, Makuuchi H, Tsuji K (1997) HLA-A2 antigen status predicts metastasis and response to immunotherapy in gastric cancer. Cancer Immunol Immunother 45:53–59PubMedCrossRefGoogle Scholar
  12. 12.
    Riely GJ, Pao W, Pham D, Li AR, Rizvi N, Venkatraman ES, Zakowski MF, Kris MG, Ladanyi M, Miller VA (2006) Clinical course of patients with non-small cell lung cancer and epidermal growth factor receptor exon 19 and exon 21 mutations treated with gefitinib or erlotinib. Clin Cancer Res 12:839–844PubMedCrossRefGoogle Scholar
  13. 13.
    Ryu KS, Lee YS, Kim BK, Park YG, Kim YW, Hur SY, Kim TE, Kim IK, Kim JW (2001) Alterations of HLA class I and II antigen expression in preinvasive, invasive and metastatic cervical cancers. Exp Mol Med 33:136–144PubMedGoogle Scholar
  14. 14.
    Schilder RJ, Sill MW, Chen X, Darcy KM, Decesare SL, Lewandowski G, Lee RB, Arciero CA, Wu H, Godwin AK (2005) Phase II study of gefitinib in patients with relapsed or persistent ovarian or primary peritoneal carcinoma and evaluation of epidermal growth factor receptor mutations and immunohistochemical expression: a gynecologic oncology group study. Clin Cancer Res 11:5539–5548PubMedCrossRefGoogle Scholar
  15. 15.
    Shen YQ, Zhang JQ, Miao FQ, Zhang JM, Jiang Q, Chen H, Shan XN, Xie W (2005) Relationship between the downregulation of HLA class I antigen and clinicopathological significance in gastric cancer. World J Gastroenterol 11:3628–3631PubMedGoogle Scholar
  16. 16.
    Thatcher N, Chang A, Parikh P, Rodrigues Pereira J, Ciuleanu T, von Pawel J, Thongprasert S, Tan EH, Pemberton K, Archer V, Carroll K (2005) Gefitinib plus best supportive care in previously treated patients with refractory advanced non–small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa survival evaluation in lung cancer). Lancet 366:1527–1537PubMedCrossRefGoogle Scholar
  17. 17.
    Vitale M, Pelusi G, Taroni B, Gobbi G, Micheloni C, Rezzani R, Donato F, Wang X, Ferrone S (2005) HLA class I antigen down-regulation in primary ovary carcinoma lesions: association with disease stage. Clin Cancer Res 11:67–72PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Kazuto Nishio
    • 1
    • 2
    Email author
  • Tokuzo Arao
    • 1
    • 2
  • Terufumi Kato
    • 1
  • Hideyuki Yokote
    • 1
    • 2
  1. 1.Pharmacology DivisionNational Cancer Center Research InstituteTokyoJapan
  2. 2.Department of Genome BiologyKinki University School of MedicineOsakaJapan

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