Τίτλος:
Tumor molecular profiling of NSCLC patients using next generation sequencing
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Tsoulos, N.
Papadopoulou, E.
Metaxa-Mariatou, V.
Tsaousis, G.
Efstathiadou, C.
Tounta, G.
Scapeti, A.
Bourkoula, E.
Zarogoulidis, P.
Pentheroudakis, G.
Kakolyris, S.
Boukovinas, I.
Papakotoulas, P.
Athanasiadis, E.
Floros, T.
Koumarianou, A.
Barbounis, V.
Dinischiotu, A.
Nasioulas, G.
Περιοδικό:
ONCOLOGY REPORTS
Εκδότης:
Spandidos Publications
Λέξεις-κλειδιά:
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
DOI:
10.3892/or.2017.6051
