Noemí Reguart1,2, Cristina Teixidó3, Ana Giménez-Capitán3, Laia Paré2, Patricia Galván2,3,4, Santiago Viteri5, Sonia Rodríguez3, Vicente Peg3, Erika Aldeguer3, Nuria Viñolas6, Jordi Remon7, Niki Karachaliou3,5,8, Esther Conde9, Fernando Lopez-Rios9, Ernest Nadal10, Sabine Merkelbach-Bruse11, Reinhard Büttner11, Rafael Rosell3,5,12, Miguel A Molina-Vila13, Aleix Prat6,2. 1. Medical Oncology, Hospital Clínic, Barcelona, Spain; nreguart@clinic.ub.es mamolina@pangaeabiotech.com. 2. Translational Genomics and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. 3. Pangaea Biotech, Laboratory of Oncology, Quirón Dexeus University Hospital, Barcelona, Spain. 4. Translational Genomics Group, Vall d'Hebron Institute of Oncology (VHIO). 5. Dr Rosell Oncology Institute, Quirón Dexeus University Hospital, Barcelona, Spain. 6. Medical Oncology, Hospital Clínic, Barcelona, Spain. 7. Department of Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France. 8. University Hospital Sagrat Cor, Barcelona, Spain. 9. Laboratorio de Dianas Terapéuticas, Centro Integral Oncológico Clara Campal, Hospital Universitario Madrid Sanchinarro, Madrid, Spain. 10. Medical Oncology Service, Catalan Institute of Oncology, L'Hospitalet, Spain. 11. Institute of Pathology, University Hospital Cologne, Cologne, Germany. 12. Cancer Biology and Precision Medicine Program, Catalan Institute of Oncology, Germans Trias i Pujol Health Sciences Institute and Hospital, Badalona, Barcelona, Spain. 13. Pangaea 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 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 (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.
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 (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.
Authors: Niki Karachaliou; Maria Gonzalez-Cao; Guillermo Crespo; Ana Drozdowskyj; Erika Aldeguer; Ana Gimenez-Capitan; Cristina Teixido; Miguel Angel Molina-Vila; Santiago Viteri; Maria De Los Llanos Gil; Salvador Martin Algarra; Elisabeth Perez-Ruiz; Ivan Marquez-Rodas; Delvys Rodriguez-Abreu; Remedios Blanco; Teresa Puertolas; Maria Angeles Royo; Rafael Rosell Journal: Ther Adv Med Oncol Date: 2018-01-18 Impact factor: 8.168