Abstract
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Purpose: We report ten novel EGFR mutations at exons18 and 21 from a series of NSCLC patients treated with gefitinib. Patients and Methods: Genomic DNA was extracted from microdissected formalin fixed paraffin-embedded tumor tissue and was amplified by nested PCR reactions for exons 18, 19, and 21 of EGFR. Sequencing was performed using forward and reverse nested primers with the ABI Prism 3100 DNA Analyzer. Results: Five novel mutations were identified in exon 18 and 5 in exon 21. Patient’s characteristics, treatment with gefitinib and outcome arepresented in the table: Patient 1, ex-smoker with squamous cell carcinoma carried a novel mutation in exon 21 and he is without disease progression after 160+ weeks with gefitinib. Patient 5 carried a novel mutation in exon 18 in primary tumor but no mutation could be detected in adrenal relapse; he achieved a PR for 146 weeks with gefitinib. Patient 3, smoker with squamous cell carcinoma, carried a novel mutation in exon 18 and was primary resistant to gefitinib. Conclusion: The detected novel mutations of EGFR could be associated with sensitivity or resistance to gefitinib. Further studies in a larger number of patients are needed. *Sq: squamous, Ad: Adenocarcinoma, OR: overall response, PR: partial response, SD: stable disease, PD progressive disease, TTP: time to tumor progression, OS: overall survival
[Proc Amer Assoc Cancer Res, Volume 47, 2006]
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