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Updated: Jan 3, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Mapping actionable pathways and mutations in brain tumours using targeted RNA next generation sequencing
Krissie Lenting1, Corina N A M van den Heuvel1, Anne van Ewijk2
1Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Geert Grooteplein 26, 6525, GA, Nijmegen, The Netherlands.
Abstract:
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.
Insights
A new targeted RNA next-generation sequencing (t/RNA-NGS) test identifies active cancer pathways for personalized treatment. This molecular profiling aids oncologists in making more accurate therapy decisions for glioma patients.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Precision cancer medicine faces challenges due to molecular heterogeneity and lack of reliable biomarkers.
- Targeted therapies are often inaccurate for individual patients because of these limitations.
- Identifying hyperactive biological pathways in individual tumors is crucial for improving treatment accuracy.
Purpose of the Study:
- To develop and validate a novel targeted RNA next-generation sequencing (t/RNA-NGS) technique for glioma.
- To assess the potential of t/RNA-NGS in providing histology-independent molecular diagnoses.
- To identify actionable molecular aberrations and therapeutic targets for personalized cancer treatment.
Main Methods:
- Application of a novel targeted RNA next-generation sequencing (t/RNA-NGS) technique to surgically obtained glioma tissues.
- The t/RNA-NGS test quantifies transcript levels and splice variants of hundreds of genes involved in key cancer pathways.
- Utilized molecular inversion probes for mutation detection and pathway activity analysis.
Main Results:
- The t/RNA-NGS technique demonstrated proof of concept, generating histology-independent molecular diagnoses for glioma.
- Identified molecular classifiers strongly associated with conventional histopathology and patient prognosis.
- Confirmed known glioma aberrations and discovered novel actionable gene expressions and mutations, suggesting drug repurposing opportunities.
Conclusions:
- The t/RNA-NGS technique offers a comprehensive molecular profiling approach for individual cancer patients.
- This method aids in identifying actionable pathways and potential therapeutic targets, improving personalized treatment strategies.
- The cost-effectiveness of t/RNA-NGS makes it a valuable tool for oncologists in therapy decision-making.
