Mapping actionable pathways and mutations in brain tumours using targeted RNA next generation sequencing

Autor: 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
Rok vydání: 2019
Předmět:
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
Zdroj: 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
ISSN: 2051-5960
Popis: 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.
Databáze: OpenAIRE
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