Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page
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Sub-category:
+ @4 o% D: _% s( {( P7 sMolecular Targets
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% P7 [4 d* C, E6 d; d" hCategory:7 X* q9 z- \" Y$ Y% ~ `% m# v9 L0 V9 J
Tumor Biology
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* `4 ~- o; ]6 K L6 H& J: tMeeting:
# i, o" O& `' n. r0 w+ o$ V3 t2011 ASCO Annual Meeting
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Session Type and Session Title:
6 t) C$ { ]% W- W, h/ |Poster Discussion Session, Tumor Biology + J/ m+ t" m7 ]4 X
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9 R7 @. h! D( K' R9 |) S2 iAbstract No:2 C/ ~' }& W2 P
10517
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Citation:
7 u0 [5 P3 W1 T* h& e1 JJ Clin Oncol 29: 2011 (suppl; abstr 10517)
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a( N) m7 m' D# e' l+ n7 g$ DAuthor(s):
! ~$ D6 s, `) }& f9 {$ m9 DJ. 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.% K" M& c- X: x' ~/ W- Z! C: Q
- d9 V( w% t5 [; ]0 a' X0 ^4 wAbstract Disclosures, ~6 V) Z Q, L( |$ b! c/ i3 ~7 {
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Abstract:
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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.
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