Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page / L3 Q8 y6 L; Q( J/ F/ q
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Molecular Targets
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Category:/ p8 w# I3 P( j- O
Tumor Biology / j' i# F$ f# U, M% k2 I( ^
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Meeting:
D" r& f! U; }2011 ASCO Annual Meeting . i7 m0 W& j, q" i9 F
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( u; c; a+ u7 J, V9 z6 m+ G0 [Poster Discussion Session, Tumor Biology 5 Z2 P; ?! v" }0 Z
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Abstract No:4 l% f5 [; b# X7 S: y- P
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J3 s* U* I- N, g2 B* t- OCitation:) X; N$ r" i; e, X
J Clin Oncol 29: 2011 (suppl; abstr 10517) ; F, J3 f9 N) i' o' E) Q! U7 q
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Author(s):; x6 H/ t# x1 K& B: }8 b' l
J. 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 9 [% r4 J8 |5 f$ w
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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.+ k, Q1 P# p. F* i! E# e; ^
. ~1 u& E5 m1 n- q$ m% jAbstract Disclosures
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Abstract:. B% \$ i4 V" M7 [5 \
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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." a2 Z$ V6 O& f, k7 @
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