Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page ) }8 B, H! Z A2 m4 G9 \; N
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Sub-category:+ _$ \8 L7 G+ y1 ?: h
Molecular Targets
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Category:
, S; f. s$ g d- Z! K4 a3 I4 yTumor Biology # H- p, T& @1 H1 N/ I% G: I
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Meeting:
' j6 {2 E9 W- M9 C7 B2011 ASCO Annual Meeting . y1 _( T( t+ h. v" G
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Poster Discussion Session, Tumor Biology 3 N3 y$ b; E0 x6 _. S
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Abstract No:
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6 _2 p% i3 |) e& i! Z( C1 ~8 pCitation:
9 G u8 G9 c- \9 \' X7 _' x5 P) F" ^J Clin Oncol 29: 2011 (suppl; abstr 10517)
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! t1 O- ^* S' L" V+ \) [Author(s):
( O/ E) {0 k% D0 n4 J2 HJ. 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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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.% H1 C8 W" |& {
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Abstract:
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. z' d$ [/ b5 J/ q+ VBackground: 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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