Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page ; u) M/ g: D9 P
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Molecular Targets
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Category:
$ P; w8 m0 {, K0 E/ i) ?Tumor Biology
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9 q# s9 z! P4 _ H1 h" ~6 X+ c/ xMeeting:
$ ~' ^5 g. H! w1 P* S, ]5 |2011 ASCO Annual Meeting % h$ o5 _ W2 r) S
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7 ?: N$ u4 P; _5 L5 r8 zPoster Discussion Session, Tumor Biology - ?2 X- T: v- C% X
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Abstract No:
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2 b$ [9 `4 j. S4 L& D. ?/ nCitation:
0 ]) s/ U& }9 Z9 iJ Clin Oncol 29: 2011 (suppl; abstr 10517)
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0 r$ i' f4 k' v" `Author(s):
) w* ]1 g( a% {) 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 ' Z5 o# C1 y5 d8 p. m) b
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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.
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0 s2 D x5 C! [- g X, S0 VAbstract:
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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.0 L# M1 f' W2 a) K2 u* v5 x
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