Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page $ E7 F; ?# C5 ~
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Molecular Targets
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Tumor Biology : R: v# d1 u! e+ n; I2 ^
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6 k/ A+ I5 J$ w# U/ ^' `+ a2011 ASCO Annual Meeting
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Session Type and Session Title:4 E' F2 E2 P- w: g2 ?9 }1 V
Poster Discussion Session, Tumor Biology ! j8 b# ?, Z* h4 U3 Y5 F$ Y
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' \; r& _) D4 SAbstract No:- e7 Y. t u# N7 S
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J Clin Oncol 29: 2011 (suppl; abstr 10517) 7 L4 ]( J7 I- K3 j N
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, F6 c! V% ]6 l( d7 S$ z5 F) M ]Author(s):
2 \6 z" ?0 j' @: T/ jJ. Yang, X. Zhang, J. Su, H. Chen, H. Tian, Y. Huang, C. Xu, Y. L. Wu; Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China; Guangdong Lung Cancer Institute, Medical Research Center of Guangdong General Hospital, Guangzhou, China; Guangdong Lung Cancer Institute, Guangzhou, China; Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China
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* ?( e/ W2 x1 S! } ]9 nAbstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^) here and in the printed Proceedings.) d+ d9 D t; F8 h- \
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Abstract Disclosures: u8 c6 ~4 d1 m B
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Abstract:
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. N" E; V. j6 J) t) [& a, S& aBackground: The fusion of the anaplastic lymphoma kinase (ALK) with the echinoderm microtubule-associated protein-like 4 (EML4) and epidermal growth factor receptor (EGFR) mutations are considered mutually exclusive. Advanced non-small cell lung cancer (NSCLC) patients with EML4-ALK did not benefit from EGFR tyrosine kinase inhibitors (TKIs). Methods: Multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) followed by sequencing was performed for EML4-ALK fusion status detection. EGFR and KRAS mutations were determined by direct DNA sequencing. Positive results of EML4-ALK fusion were also confirmed by RACE-coupled PCR sequencing. Results: From April 2010 to January 2011, 412 patients (398 with NSCLC; 14 with SCLC) were tested for mutation status of EGFR, KRAS and EML4-ALK respectively. Frequency of EML4-ALK fusion was 10.6% (42/398) in NSCLC patients. No patients with SCLC were found to have positive EML4-ALK fusion. Frequency of concomitant EGFR and EML4-ALK gene mutations was 1.0% (4/398) in NSCLC patients, and their variants of EML4-ALK gene mutations were Variant 1 (3 patients) and Variant 6 (1 patient); being never smokers, all of them were diagnosed with advanced (3 with stage †W and 1 with stage IIIB) adenocarcinoma harbouring wild type KRAS. Two female stage †W patients with double gene mutations (1 with L858R and Variant 1; 1 with exon19 deletion and Variant 6) received first-line gefitinib which is one kind of EGFR TKIs and achieved partial response. Conclusions: Though being rare events, NSCLC patients harbouring concomitant EGFR mutation and EML4-ALK gene fusion are sensitive to first-line EGFR TKIs. Whether they could also benefit from ALK inhibition after failure to EGFR TKIs warranted further investigation.
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