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

Noemí Reguart, Cristina Teixidó, Ana Giménez-Capitán, Laia Paré, Patricia Galván, Santiago Viteri, Sonia Rodríguez, Vicente Peg, Erika Aldeguer, Nuria Viñolas, Jordi Remon, Niki Karachaliou, Esther Conde, Fernando Lopez-Rios, Ernest Nadal, Sabine Merkelbach-Bruse, Reinhard Büttner, Rafael Rosell, Miguel A. Molina-Vila, Aleix Prat

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

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    Résumé

    Background: Anaplastic lymphoma receptor tyrosine kinase (ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1), and ret proto-oncogene (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, but 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(RTPCR). 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 fusionpositive 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.

    langue originaleAnglais
    Pages (de - à)751-760
    Nombre de pages10
    journalClinical Chemistry
    Volume63
    Numéro de publication3
    Les DOIs
    étatPublié - 1 mars 2017

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