Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page
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Sub-category:, p7 G7 T4 _8 ?* O
Molecular Targets & J: p P6 \$ e% ~/ U# R/ Y0 L3 f
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Category:
- W3 i( p& Z, xTumor Biology
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Meeting:
! O; ^/ p0 x7 _2011 ASCO Annual Meeting
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Session Type and Session Title:
2 L- q; z$ D( {8 p0 u: E) PPoster Discussion Session, Tumor Biology
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Abstract No:
8 m3 n9 H; f! J; W10517
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Citation:
& D2 D: ^: G) Y6 X& F* Q+ f/ jJ Clin Oncol 29: 2011 (suppl; abstr 10517)
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Author(s):
; U+ o+ c& ^4 r6 ], t, e+ eJ. 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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4 u5 A$ W9 F$ X3 X$ K8 jAbstracts 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.
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0 T3 u: R3 K- lAbstract Disclosures: T( [& i! L2 }. h& t' W2 W; u
3 ^ B: W$ B" ~* r% WAbstract:+ J% U9 w3 n. Q7 a8 S
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* t* N2 I7 t+ @& i1 r0 i* n1 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.
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