Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page
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Sub-category:
' |$ n9 g, W+ S5 F" @' XMolecular Targets 4 N# P9 x5 a# ^) Y6 r$ I- ^
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Category:+ R% B: n" |8 R% @1 N4 s# \1 D! n
Tumor Biology
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Meeting:$ t0 ^/ [" G" n7 Y( ~* q
2011 ASCO Annual Meeting 8 U4 S( E$ v' g, p- N3 v5 b8 K
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$ B7 s: O5 h% q+ i7 k0 f% E, KPoster Discussion Session, Tumor Biology " ~! y/ [; \9 X: E' k5 u
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Abstract No:' F' \6 T! ^" y" \# J/ h
10517
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Citation:. z' j+ S/ k8 t! e
J Clin Oncol 29: 2011 (suppl; abstr 10517) 3 T5 E! P: K% b. y; W: @
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Author(s):
0 P/ S3 G( I; X. z- J# b: q1 JJ. 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 + {, j$ i7 m: W9 |: P0 P( O
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0 M3 m* X, Q( ]! ^9 ~& k" IAbstracts 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.( y# l3 c& M/ ~% S/ f1 `
1 h3 m4 x) t: c: |+ Z7 W+ v) t) JAbstract Disclosures. P8 u9 e; e! z5 X3 s6 c/ o% h$ L
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Abstract:/ v: t& `. q% n8 W- N
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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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