Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page
4 A1 ?3 u1 s6 P9 E3 G8 W5 c8 M7 Y: E6 G9 j5 @& o* [
- Y! [- t2 H3 s3 A5 E8 Q+ |' H* OSub-category:% Z/ c' s! p- e% z
Molecular Targets 6 s/ }' }7 l/ F4 y* \, E
" G! b9 r7 {7 t4 a' s
% u+ {1 G9 Q) S2 OCategory:
3 h& J1 ^, w! e. `3 PTumor Biology
: L( O1 u; D- W# P* @/ u- t4 s# a# {9 \: O
8 z: }( R8 e& n, c# @Meeting:
8 h6 Y" P! \+ x2011 ASCO Annual Meeting
" c6 Z8 E3 G5 L# s
3 m! G, N- |, ^6 J, p" N& ^$ g
o& }/ [! ]6 ?# A" T W3 O9 i7 rSession Type and Session Title:
5 @' {+ G. p& \, x* b* `" b% N# L$ pPoster Discussion Session, Tumor Biology ' i# n( ^9 G0 E2 d! V# y$ y- v
: l D8 z/ k) e6 _8 n. h( K9 ~
2 o, C0 [3 L2 d. C9 `( E8 i
Abstract No:2 ~" [* [9 t8 U& T( A) r2 {
10517
& k6 t, Q9 S5 y0 z9 X5 e, Z( L5 L" h. T' @
6 c6 \# l$ g, j! E3 I5 RCitation:- K6 D. w- t* D: _5 _. H* ~% O& V
J Clin Oncol 29: 2011 (suppl; abstr 10517) 4 n& ~" l2 l9 o2 m V9 {) }9 s
- B Q7 W1 e+ {9 k+ O W' @
, |7 A& m3 V ]! vAuthor(s):* ?0 v# t, K8 g1 N
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 ' j$ |2 u3 C$ |! y5 C
3 p1 x6 ^8 D% ^' ^
. R4 I3 j" }$ S+ B
g2 v9 y; m0 g' [' H6 QAbstracts 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.! T0 a; S3 G7 [4 i
?" C. K: {% d+ W, D
Abstract Disclosures( U; _/ S+ a' w U- O
, ^, C) P: | H' @9 F' P* n
Abstract:
+ l: n& ~6 u' v8 [) N3 V2 W$ A; T. z- ]+ {5 D
( z/ @; [5 Y( t# }+ S1 B1 M* h
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.
6 t' J4 D1 y# q4 a
. ~: J5 y C4 l* z5 O" C# J 7 y, ]9 b' \6 _% N. a$ F# j2 m
|