Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page
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Sub-category:
2 X6 d, f0 O: j/ `) q% G+ kMolecular Targets
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6 m0 H+ ~0 D1 J; K; b6 y. R+ WCategory:
; t% E! j! w2 zTumor Biology
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Meeting:5 }9 s, k, f5 c( I9 f; Z! X
2011 ASCO Annual Meeting 4 H) L& d5 F# G: D3 _, L* B" T
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4 _% ~: R3 Z! `Session Type and Session Title:
6 A' F0 M7 M1 }* v6 s& z! wPoster Discussion Session, Tumor Biology # u* V% o3 P" j) E% c
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Abstract No:
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J Clin Oncol 29: 2011 (suppl; abstr 10517) 5 O. X8 N+ |8 I4 ?. v
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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 ( y) W D: g) u# }7 V4 Z" F! k) ` o
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6 Q8 r, F& ` t ~* dAbstracts 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.5 C( C5 b7 D$ n; B: a# O
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Abstract Disclosures" R* Q1 b! t5 y, X5 ]& F2 W) G
* R/ F9 t6 W: i8 p2 I$ XAbstract:
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9 S/ f) _' e( Q( ^. q% PBackground: 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.: V2 l8 y% V% b2 P
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