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Clin Chem. 2017 Jan 10. pii: clinchem.2016.265314. doi: 10.1373/clinchem.2016.265314. [Epub ahead of print]

Identification of ALK, ROS1 and RET Fusions by a Multiplexed mRNA-Based Assay in Formalin-Fixed, Paraffin-Embedded Samples from Advanced Non-Small-Cell Lung Cancer Patients.

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  • 1Medical Oncology, Hospital Clínic, Barcelona, Spain;
  • 2Translational Genomics and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
  • 3Pangaea Biotech, Laboratory of Oncology, Quirón Dexeus University Hospital, Barcelona, Spain.
  • 4Translational Genomics Group, Vall d'Hebron Institute of Oncology (VHIO).
  • 5Dr Rosell Oncology Institute, Quirón Dexeus University Hospital, Barcelona, Spain.
  • 6Medical Oncology, Hospital Clínic, Barcelona, Spain.
  • 7Department of Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
  • 8University Hospital Sagrat Cor, Barcelona, Spain.
  • 9Laboratorio de Dianas Terapéuticas, Centro Integral Oncológico Clara Campal, Hospital Universitario Madrid Sanchinarro, Madrid, Spain.
  • 10Medical Oncology Service, Catalan Institute of Oncology, L'Hospitalet, Spain.
  • 11Institute of Pathology, University Hospital Cologne, Cologne, Germany.
  • 12Cancer Biology and Precision Medicine Program, Catalan Institute of Oncology, Germans Trias i Pujol Health Sciences Institute and Hospital, Badalona, Barcelona, Spain.
  • 13Pangaea Biotech, Laboratory of Oncology, Quirón Dexeus University Hospital, Barcelona, Spain;



Anaplastic lymphoma receptor tyrosine kinase (ALK), ROS protooncogene 1, receptor tyrosine kinase (ROS1), and ret protooncogene (RET) fusions are present in 5%-7% of patients with advanced non-small-cell lung cancer (NSCLC); their accurate identification is critical to guide targeted therapies. FISH and immunohistochemistry (IHC) are considered the gold standards to determine gene fusions, they have limitations. The nCounter platform is a potentially useful genomic tool for multiplexed detection of gene fusions, but has not been validated in the clinical setting.


Formalin-fixed, paraffin embedded (FFPE) samples from 108 patients with advanced NSCLC were analyzed with an nCounter-based assay and the results compared with FISH, IHC, and reverse transcription PCR (RT-PCR). Data on response to fusion kinase inhibitors was retrospectively collected in a subset of 29 patients.


Of 108 FFPE samples, 98 were successfully analyzed by nCounter (91%), which identified 55 fusion-positive cases (32 ALK, 21 ROS1, and 2 RET). nCounter results were highly concordant with IHC for ALK (98.5%, CI = 91.8-99.7), while 11 discrepancies were found compared with FISH (87.5% concordance, CI = 79.0-92.9). For ROS1, nCounter showed similar agreement with IHC and FISH (87.2% and 85.9%), but a substantial number of samples were positive only by 1 or 2 techniques. Of the 25 patients deriving clinical benefit from fusion kinase inhibitors, 24 were positive by nCounter and 22 by FISH.


nCounter compares favorably with IHC and FISH and can be used for identifying patients with advanced NSCLC positive for ALK/ROS1/RET fusion genes.

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