Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page ' i4 X! X. O6 X0 p# ?
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Sub-category:; G8 q# b" ]# W- n+ s; ?/ x; E
Molecular Targets 1 M, y$ i( P# B" m- H
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Category:
/ ?1 w2 Z! O% H% S! gTumor Biology
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Meeting:( h d8 W$ }, S) I* ~, P$ n3 Z6 I
2011 ASCO Annual Meeting 4 O) U: U6 |: f
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Poster Discussion Session, Tumor Biology
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4 h/ b7 g4 O# h2 \9 O) UAbstract No:: Q) ?2 {" p. o1 K- b
10517 3 i* A8 \1 }0 m3 V, @6 ?
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J Clin Oncol 29: 2011 (suppl; abstr 10517) 4 l- S: S) r4 a; R7 v+ w* l# L. D e6 t
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Author(s):0 Z/ [1 Z+ d' [9 p- f# i% ^5 q# C
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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# F1 ~. y( q, q& i' vAbstracts 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 Disclosures1 [' n. U1 b2 W+ l
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Abstract:( [/ d/ K# V5 @/ q' A: q
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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.
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