Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page
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Molecular Targets
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Tumor Biology
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Meeting:
) Z# \, ]+ Q9 x- N2011 ASCO Annual Meeting
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Session Type and Session Title:
7 h6 x) H, y3 j1 g: ZPoster Discussion Session, Tumor Biology 8 \) O" U0 F$ ~, Q- I# N( `
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Abstract No:2 W0 J* F5 W4 ?. g7 M
10517
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$ M' e* g& n/ U/ HCitation:
" P) w/ Q, V8 g) [1 i, d cJ Clin Oncol 29: 2011 (suppl; abstr 10517) # `9 T$ b3 v& z* Z+ _+ I5 j8 l+ n/ j( {
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' |/ B( \: u) {' L; P$ lAuthor(s):
) G/ R! t0 ?8 X; h. T2 qJ. 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 5 N) f9 H6 V4 X# G) {4 T
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2 ^2 D* h4 C$ z- z/ UAbstracts 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.; Y: _/ ]4 _* P, W4 X! M% L
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Abstract Disclosures0 V- J" E0 F, `5 @6 H8 H; p. u
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9 W0 B7 z$ `/ U8 b( nBackground: 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.! i0 s) ~% M& |2 q$ T* ^# y/ p
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