Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page : i7 @, R; d/ Y4 m* m" Q- ^
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Sub-category:
' L; X8 F% S/ zMolecular Targets 0 }% y" o# I K4 _0 @! C/ S
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Category:
) u, k3 B, K" G5 J9 n$ ~/ BTumor Biology
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Meeting:) G& @, m) a( M6 l. E+ t- v
2011 ASCO Annual Meeting
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Session Type and Session Title:$ ~3 z& `' Z8 S
Poster Discussion Session, Tumor Biology 7 T, x# J }7 b1 M( U; Z& I% \% q
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Abstract No:! i7 N! m, q$ s
10517
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Citation:! ^+ v& f8 _9 \5 I4 s3 E" L
J Clin Oncol 29: 2011 (suppl; abstr 10517) ! A! C8 D# A9 T, e
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) Z" v' Z5 B" {. m% y, u2 p/ 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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' l, z5 o% J, g& H+ L+ E3 s# UAbstracts 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.8 ^2 H# G( I6 q6 B: \2 ^
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( X5 s2 T4 @& |# z# ~# Y; TAbstract:
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4 A3 n9 X$ S1 ~ ~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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