Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page 6 D) Y0 I5 ^1 [) B( V l
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Sub-category:6 W3 S; V7 B$ u0 I @4 H2 p$ m
Molecular Targets 7 G6 B5 v3 Y, u! a7 T
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Tumor Biology 6 {( y. `: M) y$ p( A; f/ G
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7 a" g) O; w: r8 q+ w( C8 yMeeting:
' a8 E8 i, F. j1 }, Y" |" S2011 ASCO Annual Meeting # T! ]) x! s! [8 F. y0 y$ _- z* n1 O
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y. q+ M7 n- p$ F, A+ cSession Type and Session Title:
; U9 Q# N: \' P6 n" OPoster Discussion Session, Tumor Biology ) B: x+ X3 \$ A, O# |& W2 V
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9 y* Y' n% E; g2 B: g3 T: c; n) gAbstract No:# t K$ F) y. g/ I4 p
10517 / r+ H1 v0 E7 m6 {2 t
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) s( ~* q- u! o: t* H( n% y2 S2 ]J Clin Oncol 29: 2011 (suppl; abstr 10517)
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Author(s): C6 B* m5 q5 \( }( t0 L d
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
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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.- v0 r* ?5 l/ r2 h0 \2 v
, C6 f9 j: K) e: a$ @, JAbstract Disclosures, [& X& Q2 G8 Q* }, V z2 j4 P
5 d3 y; K2 o6 {* o- i$ ]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.
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