Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page 4 d# P2 ?! ]- m; ?% N. b/ ~8 [( U
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Sub-category:
9 `" K6 m, m8 q1 N EMolecular Targets
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Category:
4 ^' A# N |, ZTumor Biology
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" a+ @9 s8 { a: A/ o2 IMeeting:
4 W" k0 o5 Z, o' a3 o1 c7 }& a2011 ASCO Annual Meeting
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2 V2 w# x3 }: I1 X+ ^' a% n( N" e$ DSession Type and Session Title:8 \7 Y6 e- w. ]% G {
Poster Discussion Session, Tumor Biology
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Abstract No: K: c: P6 S: c9 c/ l
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J Clin Oncol 29: 2011 (suppl; abstr 10517) ) q1 i0 |, I4 Y! U4 T" V5 J/ J
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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 & e( y8 T. Q p! u5 U- l
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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.( F9 S* }0 J% c8 O9 g& [4 \
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Abstract Disclosures4 \1 x% _) @- |9 K6 z% s
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" V* _0 H* H6 T5 v* P. t4 }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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