title: EML4-ALK fusion lung cancer: a rare acquired event.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, NY, USA.
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Wagner
authors.forename: Francesca
authors.initials: F
authors.lastname: Demichelis
authors.forename: Rohit
authors.initials: R
authors.lastname: Mehra
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lafargue
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Moss
authors.forename: Stefanie
authors.initials: S
authors.lastname: Arbogast
authors.forename: Alex
authors.initials: A
authors.lastname: Soltermann
authors.forename: Walter
authors.initials: W
authors.lastname: Weder
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Giordano
authors.forename: David G
authors.initials: DG
authors.lastname: Beer
authors.forename: David S
authors.initials: DS
authors.lastname: Rickman
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
mesh_terms: 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
chemical_list: 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