Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page " Q% V" C) `7 w5 ?5 Q: R8 Q; H" ?
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Sub-category:
( z0 [9 v( B) K) M) S. U7 ~Molecular Targets 7 T( a, Y" [; s+ _! B! _
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^$ ?! g1 R9 F9 E* p: C" @Tumor Biology 7 ~ `% W2 h$ |; m- \' F2 C4 N
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Meeting:
& A! N$ n+ p+ [) {% b. w4 E: t4 h2011 ASCO Annual Meeting 0 o5 G9 U8 }" X7 N! H
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Poster Discussion Session, Tumor Biology ; e2 ]# k b! k$ Y9 i. E5 Q n H* p
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J Clin Oncol 29: 2011 (suppl; abstr 10517)
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Author(s):
) o# Z6 ^0 U7 p. ~: DJ. 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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Abstracts 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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( g- W/ \7 Z$ [ v6 i; ^9 SAbstract:' A* H: _4 \+ }* V5 @; o2 X% S" |0 T7 b$ ]
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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.2 V( ?' c: q6 S$ p% v
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