Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page
, u( n$ B; ?& B3 Z5 R3 \, G, y$ H3 M0 H5 i3 d- D; S
$ c( \' }4 `1 @' T/ d+ vSub-category:
% f: L! m. d D) w: e$ g% |Molecular Targets ( ]/ `: P% O1 @
! i# P: J- @1 [* \7 a# D- ^
& J( f6 V( ], ~3 R7 t. A3 S2 y& ~
Category: |8 @5 C! |2 }( @1 W4 l( P4 w
Tumor Biology
8 _# f$ A/ w3 {0 ~: B7 J, w: I$ i M9 f7 v, K6 j9 c5 d5 i, n& A
& X* k3 n1 \; I2 h6 \ J$ o, c
Meeting:7 F! K* g p5 D; M) h
2011 ASCO Annual Meeting 8 N( w5 _" O, I4 e% ]- }
5 O" @8 t- T' J; p
) B9 d! G! g/ B; `: B5 f- L
Session Type and Session Title:0 w6 n: D" M$ `% s1 @ b
Poster Discussion Session, Tumor Biology
8 W. s( y Y5 t! g& q. X& F8 N$ \
% S" x1 o- j# _2 J( o& o) j, n2 l8 e- }8 p: k& V2 [) k1 M0 r
Abstract No:. g9 K' q( A+ h o6 C+ r
10517 ( _; L2 w- k1 x
8 G% m! y; G& X& t# l
; {7 n$ h5 a! W# \) @9 A. kCitation:
0 c+ X3 E9 U$ RJ Clin Oncol 29: 2011 (suppl; abstr 10517)
: K% M) x5 A) d3 O" Z+ d- T; H
: a/ K3 z' o$ E6 y4 b4 D, }0 S. ~' _( t, T
Author(s):
* _4 u$ G: ^; f& f$ lJ. 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 , h O( w- N) _ A* U) r) r6 q
! `% T2 P; M/ q$ v. m7 J6 D
2 o+ A. i0 y3 a9 n! ?& c9 F" A; Z, f% \; {) a6 H6 h$ k3 ?. U
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.' p- o" G" i+ Z
+ q1 G5 D0 l, @+ W: B0 AAbstract Disclosures1 r: Z$ {- {8 z* x/ e/ G$ ^
# M/ U% [& a0 W- V1 q" Q
Abstract:
4 B& l: B9 V0 R) W& \9 _( W. C; u0 U! S0 Z' V
' @8 U0 [6 N; n, b
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.
0 @* A4 B2 J' t. t6 j0 K9 W4 a. \0 W4 I# |# ~- `0 [" ^% Z7 b: [
% s/ T% u0 z/ _7 Q8 ^
|