Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page / K9 \ x' i% R' Z5 _; r
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Sub-category:
/ c: Q8 x; o2 K5 nMolecular Targets
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Category:
[% }% |* z4 c3 R: B0 r! E# [0 z JTumor Biology
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# {2 J% [9 X7 @: U2 F' j9 W0 e8 ^& QMeeting:
; c* I4 L7 F( T9 [2011 ASCO Annual Meeting 9 A$ u1 H% s- s% A& D' a, m% m8 f% z* C" n
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Session Type and Session Title:
5 n/ A$ f, b9 I$ m( fPoster Discussion Session, Tumor Biology
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Abstract No:4 K# }: a9 ?- I/ j
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Citation:
) v9 D+ `5 z+ DJ Clin Oncol 29: 2011 (suppl; abstr 10517)
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Author(s):
) O) v4 l( }4 y" ^# `* WJ. 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 - E. V" A# }2 b& p/ S! }
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( T T- d1 W( oAbstracts 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.
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Abstract Disclosures
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Abstract:% f6 a4 v4 `9 a8 q9 W3 K) C: d
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/ d! K# t3 [& c4 l5 D/ }* O2 QBackground: 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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