TY - JOUR
TI - Tumor molecular profiling of NSCLC patients using next generation sequencing
AU - Tsoulos, N.
AU - Papadopoulou, E.
AU - Metaxa-Mariatou, V.
AU - Tsaousis, G.
AU - Efstathiadou, C.
AU - Tounta, G.
AU - Scapeti, A.
AU - Bourkoula, E.
AU - Zarogoulidis, P.
AU - Pentheroudakis, G.
AU - Kakolyris, S.
AU - Boukovinas, I.
AU - Papakotoulas, P.
AU - Athanasiadis, E.
AU - Floros, T.
AU - Koumarianou, A.
AU - Barbounis, V.
AU - Dinischiotu, A.
AU - Nasioulas, G.
JO - ONCOLOGY REPORTS
PY - 2017
VL - 38
TODO - 6
SP - 3419-3429
PB - Spandidos Publications
SN - 1021-335X
TODO - 10.3892/or.2017.6051
TODO - 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
TODO - 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.
ER -