Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page ; J5 v' _+ n6 o) R! U3 v
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Sub-category:5 @( X8 R0 m! m( I @& n3 h
Molecular Targets
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Category:
# F) w0 | x; S9 V8 xTumor Biology
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Meeting:
0 s# q4 l6 l1 e. H* i: u5 Y2011 ASCO Annual Meeting 2 d$ q0 g( C* j; v: l, |6 @' ~
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Session Type and Session Title:
9 L: k( A+ T' ]8 N3 ~! k7 F( [Poster Discussion Session, Tumor Biology
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Abstract No:( l1 i& M! h1 L6 B
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1 ^2 b& T# D4 _* y# qCitation:
$ `4 o0 ?+ g: w$ d8 LJ Clin Oncol 29: 2011 (suppl; abstr 10517)
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Author(s):
& k- P9 \9 P4 W) M0 i- 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 . \% A5 C8 |- C% ~
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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.: w' `0 x( N- e! X6 G5 P
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Abstract Disclosures! Z8 x9 u; K& o: B
! `9 W9 P6 R- e2 u; U4 h2 nAbstract:
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. l5 ?" k2 C2 R# w0 zBackground: 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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