Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page : L+ ]9 X1 u% K6 G2 \
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Molecular Targets % a3 s4 t4 ^: \- ~& S, t6 z
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Category:$ h* A1 A5 P! ^- ]
Tumor Biology $ x6 k" h! _% b" L# U% Q1 f; s
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Meeting:
- i7 _9 s# { m( Y+ w! W2011 ASCO Annual Meeting
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Session Type and Session Title:6 O f) @% n- K" ]: i1 I8 q7 ]
Poster Discussion Session, Tumor Biology
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Abstract No:; q, `; b( M& _% h6 Y; x
10517
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; M: S e5 @- |* X& NCitation:
& N* ?/ @& Z7 \# i- TJ Clin Oncol 29: 2011 (suppl; abstr 10517)
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Author(s):* g9 q9 l6 h. ^+ ]4 Z( z0 v
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 4 k a6 D/ e/ { S/ u' x
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8 k- Y" K% Q$ \! i& ~ ~' 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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1 Z/ @/ i7 h/ s6 h. nAbstract Disclosures! m7 I v# N+ H
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$ N2 K+ Y- ^9 W% S, F ]; _Background: 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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