Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page 8 W- I# _0 \# h; |# X
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Molecular Targets , ]. t6 _4 b3 \! v- M6 t
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Category:
0 k7 a7 P" J: K; _9 J4 R" v( ^* mTumor Biology
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2011 ASCO Annual Meeting
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; a6 Q4 |! _3 _Poster Discussion Session, Tumor Biology
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8 x+ G3 ]7 U5 X, f, F( n$ EAbstract No:
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" |) J' ^$ m0 [! I: r" WCitation:
- E! ?* K4 y' B3 f! T& O7 @( Q# TJ Clin Oncol 29: 2011 (suppl; abstr 10517)
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Author(s):: ]# @: y2 L6 z1 W2 h- e5 W, Y: ?
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 & |( x. j5 p X0 ^
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+ k8 w" w8 N; ~; d5 U- d" f% Y: TAbstracts 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.- b2 o9 [: z- @5 c7 [
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X, {0 @( p% I: C& j$ aBackground: 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.3 P. s2 E f$ t+ @+ G9 a* b! V9 u b
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