Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page 1 p0 l- q; k, l% v4 S+ D1 q* |
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$ q3 {6 W& d6 K. OSub-category:
3 H# S3 I" f5 ?# K" KMolecular Targets
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Category:
+ b+ J1 n7 ?4 t3 wTumor Biology
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Meeting:
( Q& k2 ^" D G1 d* e( s- p0 j# Y+ p2011 ASCO Annual Meeting
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Session Type and Session Title:, I, e- E% S1 ?7 B) _) L
Poster Discussion Session, Tumor Biology
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Citation:5 w, V* b. Q4 f6 C5 o, r' [% k
J Clin Oncol 29: 2011 (suppl; abstr 10517) 0 W2 W i# n$ z
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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 + }$ }. r7 E' a' l" k
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! ^/ u& b4 s$ e2 QAbstracts 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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/ R e' T- ` Y( c" A! P3 ^Abstract Disclosures8 Q8 E! f; k7 d c# m; [# C) m
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Abstract:/ ^+ y( G; e1 W; P( @; i9 N% S( t& q
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/ a; i% l# N" _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.4 ^; c+ I- m8 w/ o
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