Mutations in the tyrosine kinase domain of the EGFR gene associated with gefitinib response in non-small-cell lung cancer
| Autor: | María del Cristo Rodríguez Pérez, Kenichi Nishiyama, Jose Miguel Sanchez, Pedro Mendez, Teresa Moran, Cristina Queralt, Yukito Ichinose, Rafael Rosell, Miquel Taron, Jose Luis Mate, Carme Sarries, Beatriz Cirauqui, Jose Javier Sanchez, Benjamin Besse, Noemi Reguart |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Pulmonary and Respiratory Medicine Cancer Research Lung Neoplasms DNA Mutational Analysis Antineoplastic Agents medicine.disease_cause Polymerase Chain Reaction Exon Sex Factors Gefitinib Carcinoma Non-Small-Cell Lung medicine Humans Epidermal growth factor receptor Lung cancer Gene Aged Laser capture microdissection Mutation biology Smoking Middle Aged Protein-Tyrosine Kinases medicine.disease Survival Analysis ErbB Receptors Treatment Outcome Amino Acid Substitution Oncology Quinazolines Cancer research biology.protein Regression Analysis Female Tyrosine kinase medicine.drug |
| Zdroj: | Lung Cancer. 50:25-33 |
| ISSN: | 0169-5002 |
| DOI: | 10.1016/j.lungcan.2005.05.017 |
| Popis: | The potential relevance of epidermal growth factor receptor (EGFR) mutations to non-small-cell lung cancer treatment has recently been identified. We have examined the presence of EGFR mutations in Japanese and Spanish gefitinib-treated non-small-cell lung cancer patients. A total of 34 gefitinib-treated patients were screened, 18 from Japan and 16 from Spain. Laser capture microdissection was performed for the accurate procurement of tumor cells. EGFR exons 18, 19 and 21 were amplified from genomic DNA by means of PCR, and the samples were then subjected to bi-directional automatic sequencing. EGFR somatic mutations in the tyrosine kinase domain were found in 8 of 34 patients (23.5%). Gefitinib response was observed in 7 of 8 patients (87.5%) with EGFR mutations and in 3 of 24 (12.5%) with wild-type EGFR (P=0.0003). Five deletion mutations were clustered in the region spanning codons 746 to 750 (ELREA) within exon 19. Three additional tumors had amino acid substitutions within exon 18, at codons 718 and 719. Logistic regression analysis showed that response was primarily linked to the presence of EGFR mutations and secondarily linked to female gender, non-smoker status and a greater number of prior chemotherapy regimens. The presence of EGFR mutations is a major determinant of gefitinib response, and EGFR tyrosine kinase inhibitors should be tested in clinical trials of first-line treatment of lung adenocarcinomas harboring EGFR mutations. |
| Databáze: | OpenAIRE |
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