Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page " Q+ m3 C7 R% {' }
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Molecular Targets , @# `. X h# h1 K. z7 W7 X
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% ^! P4 i* W# A5 {1 w+ Z3 Y! |( \Tumor Biology
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Meeting:' _( O; ^0 V, C1 `3 p0 |
2011 ASCO Annual Meeting & K( m& e# y6 u1 O9 u; K$ F# [
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Poster Discussion Session, Tumor Biology # O; B5 N9 P' f1 I* ?6 T
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8 j$ ?' W7 _7 \( d# K* gAbstract No:, C1 w$ D/ I# i# \
10517 9 w# w& d0 s, o/ P% P0 Q
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( f/ R6 u. N+ ~" V; w* Y# n* ICitation:2 ^9 ^. C( w( D X, t
J Clin Oncol 29: 2011 (suppl; abstr 10517) " @1 q* e; W! [5 y' n4 w2 R1 e
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Author(s):
: I% ]( `) E* \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
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$ c4 P$ D+ p& B' B4 {3 oAbstracts 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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Abstract:. N! Y8 A: O6 D( H0 ]0 t
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2 ~: H1 a6 A5 g; QBackground: 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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