Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page ; G& T8 l) p" a1 e& ^! |+ k
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Sub-category:
$ f0 i b6 a5 d/ r2 n, qMolecular Targets ! {" L; X3 e# f3 o
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Tumor Biology
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Meeting:# U R4 D/ w8 {- p( n
2011 ASCO Annual Meeting
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3 _2 `' c* s" G: }$ l p- I$ JSession Type and Session Title:
5 b* J/ ?+ G: Z1 b% S/ X* YPoster Discussion Session, Tumor Biology 6 p6 D! v! @% }, Q! V {3 k/ L
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. @% n9 `, X; J$ s; q3 VAbstract No:
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J Clin Oncol 29: 2011 (suppl; abstr 10517) ! {: D2 T0 Z7 z8 T! w. J
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6 n0 D& F! ^ Q8 Y6 [- a" j. 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
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' L) i3 w- D; g2 U) _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.& \0 j; a/ v. P
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Abstract Disclosures, t$ }3 g4 l4 c w! {
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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.$ {/ k& n9 W _
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