Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page . G7 W. ?: `+ a4 i: ?
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Sub-category:7 S, R$ |) Y' a& `( |* _
Molecular Targets `$ s$ ]2 j( W
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Tumor Biology
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2011 ASCO Annual Meeting
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Session Type and Session Title:
7 y) N4 Y4 Y$ u( _; n) vPoster Discussion Session, Tumor Biology
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" o2 v9 L$ o3 Q/ B/ e: LAbstract No:8 O/ R6 P! L8 m; m5 \- B2 [
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Citation:; w& `: Z& _* I$ R
J Clin Oncol 29: 2011 (suppl; abstr 10517) " @0 X$ Q. S7 @ A6 \' x' L$ Z! B/ A
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Author(s):
% r3 ^, ` [) B9 k4 b" h$ K5 MJ. 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.& T2 r" b/ M" A
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Abstract Disclosures+ v& h f8 A7 |. ~4 C
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2 j: S# a) s0 i/ f8 HBackground: 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.! L/ q9 ^, d4 K" ~1 _# f
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