This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sasaki, H. Articles by Fujii, Y. Search for Related Content PubMed PubMed Citation Articles by Sasaki, H. Articles by Fujii, Y.

EGFR Mutation Status in Japanese Lung Cancer Patients: Genotyping Analysis Using LightCycler

Authors' Affiliations: ¹ Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan and Departments of ² Surgery and ³ Internal Medicine, National Hospital Organization, Kinki-chuo Chest Medical Center, Sakai, Japan

Requests for reprints: Hidefumi Sasaki, Department of Surgery II, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan. Phone: 81-52-853-8231; Fax: 81-52-853-6440; E-mail: hisasaki{at}med.nagoya-cu.ac.jp.

Purpose: Recently, somatic mutations of the epidermal growth factor receptor (EGFR) gene were found in 25% of Japanese lung cancer patients. These EGFR mutations are reported to be correlated with clinical response to gefitinib therapy. However, DNA sequencing using the PCR methods described to date is time-consuming and requires significant quantities of DNA; thus, this existing approach is not suitable for a routine pretherapeutic screening program.

Experimental Design: We have genotyped EGFR mutation status in Japanese lung cancer patients, including 102 surgically treated lung cancer cases from Nagoya City University Hospital and 16 gefitinib-treated lung cancer cases from Kinki-chuo Chest Medical Center. The presence or absence of three common EGFR mutations were analyzed by real-time quantitative PCR with mutation-specific sensor and anchor probes.

Results: In exon 21, EGFR mutations (CTG CGG; L858R) were found from 8 of 102 patients from Nagoya and 1 of 16 from Kinki. We also detected the deletion mutations in exon 19 from 7 of 102 patients from Nagoya (all were deletion type 1a) and 4 of 16 patients from Kinki (one was type 1a and three were type 1b). In exon 18, one example of G719S mutation was found from both Nagoya and Kinki. The L858R mutation was significantly correlated with gender (women versus men, P < 0.0001), Brinkman index (600 versus 600>, P = 0.001), pathologic subtypes (adenocarcinoma versus nonadenocarcinoma, P = 0.007), and differentiation status of the lung cancers (well versus moderately or poorly, P = 0.0439), whereas the deletion mutants were not. EGFR gene status, including the type of EGFR somatic mutation, was correlated with sensitivity to gefitinib therapy. For example, some of our gefitinib-responsive patients had L858R or deletion type 1a mutations. On the other hand, one of our gefitinib-resistant patients had a G719S mutation.

Conclusions: Using the LightCycler PCR assay, the EGFR L858R mutation status might correlate with gender, pathologic subtypes, and gefitinib sensitivity of lung cancers. However, further genotyping studies are needed to confirm the mechanisms of EGFR mutations for the sensitivity or resistance of gefitinib therapy for the lung cancer.

Key Words: EGFR • Lung cancer • Mutations • LightCycler • Genotyping

This article has been cited by other articles:

				T. Fukui, Y. Ohe, K. Tsuta, K. Furuta, H. Sakamoto, T. Takano, H. Nokihara, N. Yamamoto, I. Sekine, H. Kunitoh, et al. Prospective Study of the Accuracy of EGFR Mutational Analysis by High-Resolution Melting Analysis in Small Samples Obtained from Patients with Non-Small Cell Lung Cancer Clin. Cancer Res., August 1, 2008; 14(15): 4751 - 4757. [Abstract] [Full Text] [PDF]

				T. Takano, Y. Ohe, K. Tsuta, T. Fukui, H. Sakamoto, T. Yoshida, U. Tateishi, H. Nokihara, N. Yamamoto, I. Sekine, et al. Epidermal Growth Factor Receptor Mutation Detection Using High-Resolution Melting Analysis Predicts Outcomes in Patients with Advanced Non Small Cell Lung Cancer Treated with Gefitinib Clin. Cancer Res., September 15, 2007; 13(18): 5385 - 5390. [Abstract] [Full Text] [PDF]

				K. Hoshi, H. Takakura, Y. Mitani, K. Tatsumi, N. Momiyama, Y. Ichikawa, S. Togo, T. Miyagi, Y. Kawai, Y. Kogo, et al. Rapid Detection of Epidermal Growth Factor Receptor Mutations in Lung Cancer by the SMart-Amplification Process Clin. Cancer Res., September 1, 2007; 13(17): 4974 - 4983. [Abstract] [Full Text] [PDF]

				T. M. Chin, D. Anuar, R. Soo, M. Salto-Tellez, W. Q. Li, B. Ahmad, S. C. Lee, B. C. Goh, K. Kawakami, A. Segal, et al. Detection of Epidermal Growth Factor Receptor Variations by Partially Denaturing HPLC Clin. Chem., January 1, 2007; 53(1): 62 - 70. [Abstract] [Full Text] [PDF]

				G. J. Riely, K. A. Politi, V. A. Miller, and W. Pao Update on Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer Clin. Cancer Res., December 15, 2006; 12(24): 7232 - 7241. [Abstract] [Full Text] [PDF]

				P. A. Janne and B. E. Johnson Effect of epidermal growth factor receptor tyrosine kinase domain mutations on the outcome of patients with non-small cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors. Clin. Cancer Res., July 15, 2006; 12(14): 4416s - 4420s. [Abstract] [Full Text] [PDF]

				Y. Yatabe, T. Hida, Y. Horio, T. Kosaka, T. Takahashi, and T. Mitsudomi A Rapid, Sensitive Assay to Detect EGFR Mutation in Small Biopsy Specimens from Lung Cancer J. Mol. Diagn., July 1, 2006; 8(3): 335 - 341. [Abstract] [Full Text] [PDF]

				H. Kimura, K. Kasahara, M. Kawaishi, H. Kunitoh, T. Tamura, B. Holloway, and K. Nishio Detection of Epidermal Growth Factor Receptor Mutations in Serum as a Predictor of the Response to Gefitinib in Patients with Non-Small-Cell Lung Cancer. Clin. Cancer Res., July 1, 2006; 12(13): 3915 - 3921. [Abstract] [Full Text] [PDF]

				A. Albini and U. Pfeffer A new tumor suppressor gene: invasion, metastasis, and angiogenesis as potential key targets. J Natl Cancer Inst, June 21, 2006; 98(12): 800 - 801. [Full Text] [PDF]

				P. A. Janne, A. M. Borras, Y. Kuang, A. M. Rogers, V. A. Joshi, H. Liyanage, N. Lindeman, J. C. Lee, B. Halmos, E. A. Maher, et al. A Rapid and Sensitive Enzymatic Method for Epidermal Growth Factor Receptor Mutation Screening Clin. Cancer Res., February 1, 2006; 12(3): 751 - 758. [Abstract] [Full Text] [PDF]