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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.

Author information

  • 1Medical Oncology, Hospital Clínic, Barcelona, Spain; nreguart@clinic.ub.es mamolina@pangaeabiotech.com.
  • 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; nreguart@clinic.ub.es mamolina@pangaeabiotech.com.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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

PMID:
28073897
DOI:
10.1373/clinchem.2016.265314
[PubMed - as supplied by publisher]
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