Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page 4 {2 Y: j$ f7 _5 a
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Sub-category:, t2 l/ E) T, M0 f
Molecular Targets 2 D& Z0 G4 U" V/ Y4 ^& N
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Category:
1 m7 X6 n4 q+ Z9 [1 w, r6 JTumor Biology
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) z1 \! Q% U8 L( eMeeting:
) e7 [& [' ?) P( U5 r+ u, _2011 ASCO Annual Meeting
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Session Type and Session Title:
- w: o, f% H1 k) }Poster Discussion Session, Tumor Biology
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Abstract No:
* @9 ?1 p: K" ~+ c! d10517 + b3 Z& V/ q: ~! H! s* k% u
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5 C; ~& t" ]) e( i% ?J Clin Oncol 29: 2011 (suppl; abstr 10517)
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" L1 v& @# }6 F; E; u# _Author(s):
3 _# Z" a6 I3 o6 e! kJ. 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 2 j3 B/ o( i. U* M( w( n4 l Y
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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.- [6 H3 y/ C+ A( a/ K9 s( n" i
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Abstract Disclosures
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Abstract:/ j6 W9 y% W# k: o& O
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5 b" M1 {7 U6 u" v$ e8 L) ]( ?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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