Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page 8 g0 i. d! X/ R
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' D6 m+ b: y6 KMolecular Targets + X! Z8 `; c! S7 d
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. z) i, q. T/ x4 p$ lTumor Biology
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. _- f+ R; T3 J$ O/ AMeeting:) Y {0 H3 A( q% ]% ?+ b
2011 ASCO Annual Meeting % r* H9 {+ [- x0 I1 z
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Session Type and Session Title:
6 T0 b6 p' Q* O& }; U: Q" `: jPoster Discussion Session, Tumor Biology : Y$ g4 D) t/ K- c) `
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Abstract No:
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Citation:# l- H6 ]9 @. x) S! w
J Clin Oncol 29: 2011 (suppl; abstr 10517) * x6 G% T2 s* G$ H; Z, x- N
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Author(s):
. I- N. V3 R# w; f# OJ. 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 1 w8 B9 L2 O' T$ {+ M1 z& w& w3 e
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" x. j5 ^4 t. I" U) m% _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.
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7 N1 k! p7 g& Q0 ]Abstract:' t, T/ F# E2 r; A! R$ k2 M
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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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