EML4-ALK fusion lung cancer: a rare acquired event.
A recurrent gene fusion between EML4 and ALK in 6.7% of non-small cell lung cancers (NSCLCs) and NKX2-1 (TTF1, TITF1) high-level amplifications in 12% of adenocarcinomas of the lung were independently reported recently. Because the EML4-ALK fusion was only shown by a reverse transcription-polymerase chain reaction approach, we developed fluorescent in situ hybridization assays to interrogate more than 600 NSCLCs using break-apart probes for EML4 and ALK. We found that EML4-ALK fusions occur in less than 3% of NSCLC samples and that EML4 and/or ALK amplifications also occur. We also observed that, in most cases in which an EML4/ALK alteration is detected, not all of the tumor cells harbor the lesion. By using a detailed multi-fluorescent in situ hybridization probe assay and reverse transcription-polymerase chain reaction, we have evidence that other, more common mechanisms besides gene inversion exist including the possibility of other fusion partners for ALK and EML4. Furthermore, we confirmed the NKX2-1 high-level amplification in a significant subset of NSCLC and found this amplification to be mutually exclusive to ALK and EML4 rearrangements.
Perner
Sven
S
Department of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, NY, USA.
Wagner
Patrick L
PL
Demichelis
Francesca
F
Mehra
Rohit
R
Lafargue
Christopher J
CJ
Moss
Benjamin J
BJ
Arbogast
Stefanie
S
Soltermann
Alex
A
Weder
Walter
W
Giordano
Thomas J
TJ
Beer
David G
DG
Rickman
David S
DS
Chinnaiyan
Arul M
AM
Moch
Holger
H
Rubin
Mark A
MA
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011336:Probability; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics
C522504:EML4-ALK fusion protein, human; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors