Gefitinib-Sensitive Mutations of the Epidermal Growth Factor Receptor Tyrosine Kinase Domain in Chinese Patients with Non–Small Cell Lung Cancer

• Published in: Clinical cancer research 2005-06, Vol.11 (12), p.4289-4294
• Main Authors: Mu, Xin Lin, Li, Long Yun, Zhang, Xiao Tong, Wang, Men Zhao, Feng, Rui E, Cui, Quan Cai, Zhou, Hai Sheng, Guo, Bing Qing
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - enzymology; Adenocarcinoma - genetics; Adult; Aged; Aged, 80 and over; Amino Acid Sequence; Antineoplastic agents; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Base Sequence; Binding Sites - genetics; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - enzymology; Carcinoma, Non-Small-Cell Lung - genetics; China; DNA Mutational Analysis; DNA, Neoplasm - chemistry; DNA, Neoplasm - genetics; EGFR-TK inhibitor; Female; gefitinib Expanded Access Programme; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - enzymology; Lung Neoplasms - genetics; Male; Medical sciences; Middle Aged; Molecular Sequence Data; Mutation; mutation incidence; Pharmacology. Drug treatments; Pneumology; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Quinazolines - pharmacology; Quinazolines - therapeutic use; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - genetics; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid; Treatment Outcome; Tumors of the respiratory system and mediastinum
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-04-2506

Purpose: Studies have shown that mutations in the epidermal growth factor receptor ( EGFR ) tyrosine kinase domain are associated with response of lung cancer to gefitinib (Iressa, AstraZeneca Corp., Shanghai, China). A higher incidence of EGFR mutation was observed in non–small cell lung cancer (NSCLC) patients of Japanese origin compared with those of American origin. However, no data about such mutations in Chinese patients with NSCLC could be obtained. Methods: Primary NSCLC tissues were obtained for analysis of mutations in exons 18 to 21 of EGFR from a total of 76 patients, of whom 54 did not receive gefitinib therapy and 22 did. PCR products were sequenced directly and mutations were confirmed by an independent PCR and sequence analysis. All types of mutation were cloned and sequenced. Results: A total of 10 types of mutation were found in the series of patients, including two different silent mutations in exon 20 from 11 patients. More than half of the silent mutations (6 of 11) in exon 20 coexisted with other mutations. Mutations were more frequent in adenocarcinoma (17 of 35; 48.6%) compared with squamous carcinoma (1 of 19; 5.3%) among untreated patients. Similar mutations were observed in all seven gefitinib-treated patients with partial response, and no mutations were detected in all eight patients with progressive disease ( P < 0.001), except two silent mutations. Three mutations were observed in seven patients with stable disease. Conclusions: Mutations in the epidermal growth factor receptor tyrosine kinase domain in lung adenocarcinomas from Chinese patients were more frequent than reported previously in lung adenocarcinomas from American patients. Such mutations were well correlated with tumor response to gefitinib.