Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page 8 ^8 H* }$ ~6 `% a, r
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Molecular Targets 0 a6 V( M- {. ?0 j, Q9 m' K
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Category:
1 A1 @7 b J# m/ p9 J* R- uTumor Biology
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Meeting:
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& v! Y- i$ }4 |" G { `1 kSession Type and Session Title:
0 y' k x) [4 EPoster Discussion Session, Tumor Biology % U5 J% u" {* w1 e+ T8 O& k) l' V; Y
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# g1 r9 H( i3 n# K* QAbstract No:, c" z9 u7 f p: X) E }+ R/ \
10517
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Citation:1 M* U' U, I2 D& r
J Clin Oncol 29: 2011 (suppl; abstr 10517) ' h3 |! M' ^: V p0 c5 d7 Z( V! J
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6 K- u D# l2 t; ^Author(s):$ S# p, z9 G/ q3 B. f+ C
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
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+ r4 Y+ z5 ~4 O- h8 PAbstracts 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.4 g, M3 i6 X9 c" W( Z8 S6 V- |
2 s6 i- n; S& I* b$ @' BAbstract Disclosures
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Abstract:
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$ G0 m+ N3 c$ M f5 rBackground: 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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