Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page 2 U# m* C1 f; M' x! }( H% b
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Sub-category:
0 e1 ]! e6 U. Y, jMolecular Targets
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' P; [; y0 L7 ^. c% t7 ATumor Biology
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Meeting:
( E6 f8 k. a/ m- F- P2011 ASCO Annual Meeting
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Session Type and Session Title:+ J5 r+ ^& |, H, _4 L9 f
Poster Discussion Session, Tumor Biology 6 @8 F$ p& h/ x4 i7 X, M1 I
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Abstract No:
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Citation:5 F/ t0 N( W. e* x2 v/ c
J Clin Oncol 29: 2011 (suppl; abstr 10517) 6 m7 F' ?1 J( a
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Author(s):
) h" g+ |0 a2 l. OJ. 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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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. Z$ Q9 y3 x, T2 T5 E
9 l3 a' O. T+ w! v3 f4 QAbstract Disclosures, g6 _8 ]7 V% v5 T1 F! _
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Abstract:3 o9 p, z- V' W- v7 d4 m! w) T
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4 j1 j+ F! g3 Z0 e8 v* Y: ]+ J3 aBackground: 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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