@article{3085784,
    title = "Tumor molecular profiling of NSCLC patients using next generation sequencing",
    author = "Tsoulos, N. and Papadopoulou, E. and Metaxa-Mariatou, V. and Tsaousis, G. and Efstathiadou, C. and Tounta, G. and Scapeti, A. and Bourkoula, E. and Zarogoulidis, P. and Pentheroudakis, G. and Kakolyris, S. and Boukovinas, I. and Papakotoulas, P. and Athanasiadis, E. and Floros, T. and Koumarianou, A. and Barbounis, V. and Dinischiotu, A. and Nasioulas, G.",
    journal = "ONCOLOGY REPORTS",
    year = "2017",
    volume = "38",
    number = "6",
    pages = "3419-3429",
    publisher = "Spandidos Publications",
    issn = "1021-335X",
    doi = "10.3892/or.2017.6051",
    keywords = "alkaline phosphatase;  B Raf kinase;  epidermal growth factor receptor;  epidermal growth factor receptor 2;  formaldehyde;  paraffin;  protein Ret;  scatter factor receptor, aged;  ALK gene;  Article;  BRAF gene;  cohort analysis;  controlled study;  decision making;  DNA determination;  EGFR gene;  ERBB2 gene;  female;  gene;  gene amplification;  gene frequency;  gene rearrangement;  gene targeting;  genetic association;  human;  informed consent;  limit of detection;  limit of quantitation;  major clinical study;  male;  MET gene;  next generation sequencing;  non small cell lung cancer;  oncogene ret;  personalized medicine;  point mutation;  priority journal;  reliability;  reproducibility;  RNA transcription;  ROS1 gene;  sensitivity and specificity;  DNA sequence;  gene regulatory network;  genetic predisposition;  genetics;  high throughput sequencing;  lung tumor;  molecularly targeted therapy;  mutation;  non small cell lung cancer;  procedures, Carcinoma, Non-Small-Cell Lung;  Female;  Gene Regulatory Networks;  Genetic Predisposition to Disease;  High-Throughput Nucleotide Sequencing;  Humans;  Lung Neoplasms;  Male;  Molecular Targeted Therapy;  Mutation;  Sequence Analysis, DNA",
    abstract = "Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and a tumor with a broad spectrum of targeted therapies already available or in clinical trials. Thus, molecular characterization of the tumor using next generation sequencing (NGS) technology, has become a key tool for facilitating treatment decisions and the clinical management of NSCLC patients. The performance of a custom 23 gene multiplex amplification hot spot panel, based on Ion AmpliSeq™ technology, was evaluated for the analysis of tumor DNA extracted from formalin-fixed and paraffinembedded (FFPE) tissues. Furthermore, the Ion AmpliSeq™ RNA Fusion Lung Cancer Research Panel was used for fusion RNA transcript analysis. The mutation spectrum of the tumors was determined in a cohort of 502 patients with NSCLC using the aforementioned targeted gene panels. The panel used for tumor DNA analysis in this study exhibited high rates (100%) of sensitivity, specificity and reproducibility at a mutation allelic frequency of 3%. At least one DNA mutation was detected in 374 patients (74.5%) and an RNA fusion was identified in 16 patients, (3.2%). In total, alterations in a cancer-driver gene were identified (including point mutations, gene rearrangements and MET amplifications) in 77.6% of the tumors tested. Among the NSCLC patients, 23% presented a mutation in a gene associated with approved or emerging targeted therapy. More specifically, 13.5% (68/502) presented a mutation in a gene with approved targeted therapy (EGFR, ALK, ROS1) and 9.4% (47/502) had an alteration in a gene related to emerging targeted therapies (ERBB2, BRAF, MET and RET). Furthermore, 51.6% of the patients had a mutation in a gene that could be related to an off label therapy or indicative for access to a clinical trial. Thus, the targeted NGS panel used in this study is a reliable approach for tumor molecular profiling and can be applied in personalized treatment decision making for NSCLC patients."
}