Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page 9 l: D) k7 d5 O7 u% a4 ]9 t! \
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Sub-category:
, B2 P0 i0 W% Z+ @Molecular Targets 4 D& p# P7 J' Y
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Category:* L+ [+ k# F1 r
Tumor Biology
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2011 ASCO Annual Meeting 6 p1 s8 q7 a7 H5 N
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Session Type and Session Title:
8 V+ `; J; c8 c- t7 E- APoster Discussion Session, Tumor Biology
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Abstract No:4 A5 [" H& e( C3 d3 o5 @
10517
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Citation:" Z( R, _* J9 d4 a) o b
J Clin Oncol 29: 2011 (suppl; abstr 10517) 7 A6 Z. t6 r$ E/ ]. o5 L$ f" ~1 a
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. [8 _% B7 c# {0 y0 YJ. 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.8 s9 b% E7 w/ E, G
8 w+ d, ]/ i# j& q7 Z+ d; s/ {Abstract Disclosures. T9 a; Y# e- n
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Abstract:
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# D, D o. m, [5 U2 q4 X% O& YBackground: 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.7 x" _. G0 [1 i" v7 N" m* W
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