Mapping actionable pathways and mutations in brain tumours using targeted RNA next generation sequencing
| العنوان: | Mapping actionable pathways and mutations in brain tumours using targeted RNA next generation sequencing |
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| المؤلفون: | Mark ter Laan, Elizabeth Tindall, Maarten te Dorsthorst, Ge Wei, Martijn A. Huynen, Duaa Elmelik, Benno Küsters, Remco de Boer, William P.J. Leenders, Anne van Ewijk, Krissie Lenting, Corina N. A. M. van den Heuvel |
| المصدر: | Acta Neuropathologica Communications, Vol 7, Iss 1, Pp 1-15 (2019) Acta Neuropathologica Communications, 7, 185 Acta Neuropathologica Communications, 7, 1, pp. 185 Acta Neuropathologica Communications |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Adult, Male, Personalized, Computational biology, Biology, DNA sequencing, lcsh:RC346-429, Pathology and Forensic Medicine, Biological pathway, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, 0302 clinical medicine, Glioma, medicine, Biomarkers, Tumor, Humans, Pathways, Gene, Diagnostics, Prognostics, lcsh:Neurology. Diseases of the nervous system, 030304 developmental biology, Aged, Single molecule molecular inversion probes, 0303 health sciences, Brain Neoplasms, Sequence Analysis, RNA, Research, Targeted RNA-sequencing, RNA, Cancer, Chromosome Mapping, High-Throughput Nucleotide Sequencing, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], Middle Aged, medicine.disease, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], 3. Good health, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Drug repositioning, 030220 oncology & carcinogenesis, Gene Targeting, Mutation, Female, Neurology (clinical), Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19], Companion diagnostic |
| الوصف: | Contains fulltext : 214227.pdf (Publisher’s version ) (Open Access) Many biology-based precision drugs are available that neutralize aberrant molecular pathways in cancer. Molecular heterogeneity and the lack of reliable companion diagnostic biomarkers for many drugs makes targeted treatment of cancer inaccurate for many individuals. Identifying actionable hyperactive biological pathways in individual cancers may improve this situation.To achieve this we applied a novel targeted RNA next generation sequencing (t/RNA-NGS) technique to surgically obtained glioma tissues. The test combines mutation detection with analysis of biological pathway activities that are involved in tumour behavior in many cancer types (e.g. tyrosine kinase signaling, angiogenesis signaling, immune response, metabolism), via quantitative measurement of transcript levels and splice variants of hundreds of genes. We here present proof of concept that the technique, which uses molecular inversion probes, generates a histology-independent molecular diagnosis and identifies classifiers that are strongly associated with conventional histopathology diagnoses and even with patient prognosis. The test not only confirmed known glioma-associated molecular aberrations but also identified aberrant expression levels of actionable genes and mutations that have so far been considered not to be associated with glioma, opening up the possibility of drug repurposing for individual patients. Its cost-effectiveness makes t/RNA-NGS to an attractive instrument to aid oncologists in therapy decision making. |
| وصف الملف: | application/pdf |
| تدمد: | 2051-5960 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::133bc99d673d3ede2a029dc9a533cd2f https://hdl.handle.net/2066/214227 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....133bc99d673d3ede2a029dc9a533cd2f |
| قاعدة البيانات: | OpenAIRE |
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