Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page & y; O9 B+ R! y3 m0 `/ g9 {8 f, U
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Molecular Targets 5 W7 y8 v: E+ A9 P( ?
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Category:9 V! ?, ?0 D5 A$ m2 t, u. T
Tumor Biology
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Meeting:
. a% a$ u0 K6 d( m5 i2011 ASCO Annual Meeting / f2 k* N$ U1 s4 i
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Poster Discussion Session, Tumor Biology ( B/ K) x9 q# \; D
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10517
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$ O6 r d, S! j$ t6 H* [8 uCitation:
5 ?9 U0 s; ]% J9 S) R" y+ xJ Clin Oncol 29: 2011 (suppl; abstr 10517)
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Author(s):) R! s9 |2 q7 b% h5 T( u- p2 Y4 T
J. 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 ; n& h( d" F- R {' g/ G5 i. V5 p
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, P1 p7 w) }) q6 Z5 B! WAbstracts 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.
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" B. U6 N" M( K$ H6 W! Z- s1 cAbstract Disclosures
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/ J C: U" {# _- m8 yAbstract:
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$ i& w8 d% N9 k0 V3 N7 l# m" nBackground: 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.0 j7 d" j2 Q; h( e' V
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