Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page
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Sub-category:7 N# E+ A3 `4 Y& s
Molecular Targets {9 N6 M9 @+ u- X7 r, j
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Category:& e% O1 Q2 c! ~1 F( x4 m+ w% a: |3 A3 I
Tumor Biology 5 R6 ?" Q5 p+ s3 k+ n: ^
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Meeting:
2 y2 @/ ^8 _3 L# J3 r" h9 g! _# \2011 ASCO Annual Meeting 8 L# v* a* e8 n# g0 o1 Z
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Session Type and Session Title:, V/ c( D: W4 a0 ]: k6 g
Poster Discussion Session, Tumor Biology
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Abstract No:, ~: x1 D( g- M* E7 T6 u/ U
10517
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- U. X7 I9 h6 \, r5 V7 UJ Clin Oncol 29: 2011 (suppl; abstr 10517)
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4 K; K0 b2 F ]9 LAuthor(s):
" O0 b4 ^. K! ]0 q' s1 ZJ. 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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& @) [. s. ?% m6 mAbstracts 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.! d8 V5 B! ]1 F; e% z
( W# p( W* ^, N( Y! W1 m1 nAbstract Disclosures. [! ?. T$ J6 a ~; n5 C
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Abstract:! W# Y* _' q$ m$ ~/ J6 h) D
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2 Q) O+ O: \5 E& M2 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.7 g* _2 Z9 h4 A8 g8 j
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