Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page
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Sub-category:
" k2 }8 g& }8 c) k- }' ^Molecular Targets
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Category:
& _0 U# k8 ^6 M' O6 \3 oTumor Biology ) C) v$ Y, u( ^- @% w% z" L& }! Y
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Meeting:
' h- ?; x$ Z( ?2 T) z# ~2011 ASCO Annual Meeting 0 t* I' k) c' Q6 |- v$ d
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Session Type and Session Title:
; {' C& ~0 c7 MPoster Discussion Session, Tumor Biology ! \1 s9 _! \3 v! O( Y, q* Z
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% F- b" t* D9 q! X$ lAbstract No:8 e$ z$ w T9 y7 c3 K9 c' t
10517
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J Clin Oncol 29: 2011 (suppl; abstr 10517) , A: \% Z- [3 Q C
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) ?" h5 I* |3 t, y: aAuthor(s):8 V5 {6 r; G/ z O/ x. A K
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 % b. J7 z6 G% V' v
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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.' D" Y- c' p8 Q7 p( U$ l- r
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Abstract Disclosures4 W* i" o# O4 Z6 X; ]* V7 g
4 i8 `, o" h s1 x5 m( GAbstract:
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: v* K7 {! f4 T: ~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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