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Detection of Copy Number Alterations Using Single Cell Sequencing
Published on: February 17, 2017
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Detection of Copy-Number Variations in CNS Tumours From Off-Target Reads of Hybrid-Capture Sequencing
Jan Schnorrenberg1, Yannis Luca Adrian1, Judith Schlathölter1
1Institute of Neuropathology, University Hospital Münster, Münster, Germany.
Neuropathology and Applied Neurobiology
|March 16, 2026
Summary
Next-generation sequencing off-target reads from small panels accurately detect copy number variations (CNVs) in central nervous system (CNS) tumors. This method provides genome-wide CNV profiles comparable to methylation arrays, enhancing CNS tumor diagnostics without extra assays.
Area of Science:
- Neuro-oncology
- Genomics
- Molecular Diagnostics
Background:
- Copy number variations (CNVs) are crucial for classifying, grading, and prognosing central nervous system (CNS) tumors.
- Genome-wide methylation arrays are standard for CNV profiling, but next-generation sequencing (NGS) panels are increasingly used.
- The utility of off-target reads from small NGS panels for CNV profiling in CNS tumors remains to be fully established.
Purpose of the Study:
- To investigate if off-target sequencing reads from small hybrid-capture NGS panels can generate clinically actionable genome-wide CNV profiles for CNS tumors.
- To compare CNV profiles derived from NGS off-target reads with those from established methylation arrays.
- To assess the diagnostic utility of this NGS-based approach in various CNS tumor types, including meningiomas and pilocytic astrocytomas.
Main Methods:
- Analyzed 60 CNS tumor samples (glioblastomas, oligodendrogliomas, ependymal tumors, medulloblastomas, choroid plexus tumors) using a small-scale custom hybrid-capture NGS panel (<0.2 Mb).
- Compared CNV profiles from NGS off-target reads with methylation array data.
- Profiled 58 meningiomas and 6 pilocytic astrocytomas with BRAF fusions using the same NGS panel.
Main Results:
- Achieved 95% concordance between NGS- and methylation-derived profiles across 527 chromosomal arm-level alterations.
- Correctly detected all 19 focal amplifications (e.g., EGFR, MYCN) and most homozygous CDKN2A/B deletions.
- Identified WHO-relevant alterations in meningiomas, supporting molecular upgrading in 16% of lower-grade tumors, and detected Chr7q focal CNVs suggestive of BRAF fusions in pilocytic astrocytomas.
Conclusions:
- Off-target reads from minimal targeted NGS panels can generate reliable genome-wide CNV profiles for CNS tumors.
- This NGS-based method offers comparable accuracy to methylation arrays without requiring additional assays or specialized probe designs.
- The findings support the integration of this approach into routine diagnostics for enhanced CNS tumor classification, grading, and prognostication.
