Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page ( I/ S' P% m1 Y9 \8 J3 l2 O
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Sub-category:
2 r. V& W3 x7 @Molecular Targets
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Tumor Biology
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/ Y( U& P T C, g$ DMeeting:
' j& N% u8 i0 L, m2 C8 N1 s2011 ASCO Annual Meeting
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Session Type and Session Title:) |) e" c$ i5 l
Poster Discussion Session, Tumor Biology ' q: l7 P% ^! Q" V, G2 c0 r `3 p/ J9 U
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Abstract No:
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/ Q0 [9 X6 Z% C2 ACitation:
! k6 L: ]8 b: w1 M4 `; n+ qJ Clin Oncol 29: 2011 (suppl; abstr 10517)
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Author(s):
6 `2 `# Y% r' c4 \' c8 MJ. 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 2 e2 K( h' \, t5 q/ ~& k) 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. Q. L2 L; B2 \% U. l4 H4 b
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Abstract:% l4 _/ G9 C; [7 I) k" V4 p
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; q! m; A8 T" d' w* _" x; 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.
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