Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page ; e, H& o6 q- Z5 a
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Sub-category:1 o# k% j: z" w% w0 h5 T
Molecular Targets , g3 x- C9 L- J/ a4 I' M1 d
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/ X/ x) M: h0 s sTumor Biology
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Meeting:
* t5 V. Z; f7 v2011 ASCO Annual Meeting
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% o: h/ f7 {: Y9 ~Session Type and Session Title:
! R, F- M( W2 ^, U6 ?Poster Discussion Session, Tumor Biology
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Abstract No:5 T- N$ P$ ~7 r- I& s( e
10517
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& q3 O5 X( G% [" N1 R( W, MJ Clin Oncol 29: 2011 (suppl; abstr 10517) 3 D4 G k2 ]! L% Y5 R
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Author(s):
5 W% X3 w5 t' S+ I! @* WJ. 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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. k ~: {" Q" z) x$ G. ~" E+ M3 N* n- oAbstracts 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.1 C% L! N0 ~4 H
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Abstract:, }! \! x2 I' J; o! O
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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.
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