P04.21 * MOLECULAR DIAGNOSTICS OF MALIGNANT GLIOMAS USING NEXT-GENERATION GENE PANEL SEQUENCING
| العنوان: | P04.21 * MOLECULAR DIAGNOSTICS OF MALIGNANT GLIOMAS USING NEXT-GENERATION GENE PANEL SEQUENCING |
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| المؤلفون: | A. Veiser, Karl Köhrer, Kerstin Kaulich, Stefanie Stepanow, Marietta Wolter, Guido Reifenberger |
| المصدر: | Neuro-Oncology. 16:ii41-ii41 |
| بيانات النشر: | Oxford University Press (OUP), 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Cancer Research, IDH1, Brain tumor, Gene mutation, Biology, medicine.disease, Molecular diagnostics, Poster Presentations, Oncology, CDKN2A, Glioma, medicine, Cancer research, Neurology (clinical), Oligodendroglioma, neoplasms, ATRX |
| الوصف: | Gliomas are histologically classified according to the World Health Organization (WHO) classification of central nervous system tumors into distinct tumor types and malignancy grades ranging from WHO grade I (benign) to WHO grade IV (highly malignant). In recent years, characteristic molecular changes were identified in the various glioma types and WHO grades. Common glioma-associated genetic alterations are mutations in IDH1 or IDH2, TP53 and ATRX in diffuse astrocytic gliomas, mutations in IDH1 or IDH2, CIC and TERT in oligodendrogliomas, mutations in TERT, PTEN, TP53 and H3F3A as well as copy number alterations of EGFR and CDKN2A/B, in glioblastomas, and mutations/genetic rearrangements of BRAF in pilocytic astrocytomas and pleomorphic xanthoastrocytomas. The identification of specific patterns of gene mutations may have diagnostic, prognostic and predictive implications for the individual patients and thus can facilitate more accurate stratification of patients to distinct treatment protocols. In this project, we therefore aimed at the improvement of the molecular diagnostics of gliomas by establishment of next-generation sequencing (NGS) of a glioma-tailored gene panel using the Ion Torrent PGM or Proton platform. For this purpose, we assembled a panel of 20 glioma-associated genes with the Ion AmpliSeqTM Desinger Tool. Our customized glioma panel includes coding sequences and hotspot regions of the genes that are most frequently mutated in gliomas. First runs were performed to determine the number of generated reads and to detect known sequence variations in several samples. To assess the specificity and sensitivity of variant detection, we compared the NGS results with conventional sequencing results and qRT-PCR data. Furthermore, the read output and variant detection of DNA libraries created from DNA extracted from frozen tissue samples and formalin-fixed paraffin-embedded tissue samples was compared. To assess the relationship of diagnostic mutation profiles with histological classification, we have screened a larger number of glioma tissue samples, including tumors of different histologies and WHO grades. Collectively, our results indicate that gene panel NGS is a robust, sensitive and specific method for the diagnostic detection of gene mutations in gliomas, which can be applied on routinely processed tumor samples in a timely and cost-saving manner. Meanwhile, we are working on the establishment of a more comprehensive glioma gene panel that will also allow for the analysis of genes less frequently mutated in glioma as well as cancer genes for which specific drugs are available, thus allowing not only for diagnostic but also also for predictive molecular testing of gliomas. Eventually, we aim to establish gene panel NGS for routine application in the molecular diagnostics of gliomas and other brain tumors. |
| تدمد: | 1523-5866 1522-8517 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9292a1288600a1085568397d5b12079dTest https://doi.org/10.1093/neuonc/nou174.153Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9292a1288600a1085568397d5b12079d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15235866 15228517 |
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