Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page " C( }$ I! N5 i4 B2 r$ ~3 n
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Sub-category:7 s, X. \/ B- [. U
Molecular Targets ; F9 u# a6 x( ^! Y
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Category:
+ ]: o7 U. f/ s. [" E9 b& H7 MTumor Biology
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Meeting:
6 y8 W. P4 s* N9 |5 ]2011 ASCO Annual Meeting
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Session Type and Session Title:
. p, [$ I8 q( h( g _, G5 [; E8 @1 aPoster Discussion Session, Tumor Biology
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) S+ j- f! \! Z: A0 ^Abstract No:
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J Clin Oncol 29: 2011 (suppl; abstr 10517) ) H" d7 j0 S: F- ~$ g' U1 O( D% g
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! a$ R! ^1 D( }' HAuthor(s):
8 e6 |5 U( B3 q0 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 % o6 {/ e+ C" X7 F+ V: B2 T, X4 O
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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.% M4 i, I% H* a r5 d* }
2 V% y. c0 z: v. eAbstract Disclosures
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9 T' ]( o2 G: g. U8 ~- `4 F$ MAbstract:1 |: M- I' w8 q- M
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7 B% ?" {7 m/ t' V9 D/ ^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.3 I2 F& w& h1 J9 x5 V3 M; @- I. z
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