Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page ' ^8 b( ?) e+ l4 S* s5 N3 _# H- J
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Sub-category:- s& [1 v" Z* k9 v' Z, p
Molecular Targets 9 y: }+ y' j' m
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Category:, t6 W! w }" T! v/ w9 e: f# m
Tumor Biology
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! {4 A# \7 b g7 s. IMeeting:# q7 U! ^, J( V) ^! j
2011 ASCO Annual Meeting
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Poster Discussion Session, Tumor Biology # P Z7 |1 S, M# s, O3 |
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Abstract No:
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, T. i' m' S5 H% @% ~- W6 Y% d! hCitation:
. A' C" Z5 h" I! O5 v, \5 zJ Clin Oncol 29: 2011 (suppl; abstr 10517)
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+ l; ~( S/ W- \. H. uAuthor(s):
' G7 J9 R, T& V0 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
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* G, x* w# {1 i* q+ _$ s- u8 }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.$ g& ]& r) o, Y* w+ o7 U
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Abstract Disclosures
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Abstract:
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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.4 M$ l: Z8 r' s
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