Long-Read Nanopore Sequencing Enhances BRCA1/2 Variant Detection Compared with Ion Torrent Analysis
Nada El Makhzen1, Brahim El Hejjioui2, Badreddine ElMakhzen2
1Ion Channels and Channelopathies Laboratory, Department of Medicine, Institute for Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, Department of Medicine, University of Bern, Bern, Switzerland; Initiative Afrique of the University of Bern, Bern, Switzerland.
The Journal of Molecular Diagnostics : JMD
|June 19, 2026
Summary
Oxford Nanopore long-read sequencing (ONT-LRS) offers comprehensive analysis of BRCA1 and BRCA2 genes. This method detects deep intronic and structural variants missed by short-read sequencing, improving breast cancer diagnostics.
Area of Science:
- Genomics
- Cancer Genetics
Background:
- Accurate detection of BRCA1 and BRCA2 variants is crucial for breast cancer diagnosis and management.
- Short-read sequencing often limits analysis to coding regions, potentially missing critical deep intronic and structural variants in these large genes.
Purpose of the Study:
- To evaluate the performance of Oxford Nanopore long-read sequencing (ONT-LRS) for comprehensive analysis of the BRCA1 and BRCA2 genes.
- To compare the diagnostic yield of ONT-LRS with standard Ion Torrent sequencing for detecting BRCA1 and BRCA2 variants.
Main Methods:
- Retrospective analysis of DNA samples from 27 breast cancer patients.
- Initial analysis using Ion Torrent sequencing followed by long-range PCR amplification and ONT-LRS on R10.4.1 flow cells.
- Comparative analysis of variants identified by both sequencing methods.
Main Results:
- High concordance was observed between ONT-LRS and Ion Torrent for exonic single-nucleotide variants.
- ONT-LRS identified additional variants missed by Ion Torrent, including a deep intronic variant affecting splicing and a structural variant.
- ONT-LRS demonstrated superior capability in detecting complex variants within BRCA1 and BRCA2.
Conclusions:
- ONT-LRS enhances diagnostic capabilities beyond short-read sequencing for BRCA1 and BRCA2 analysis.
- This technology enables accurate detection of deep intronic and structural variants, which may have significant implications for patient management and hereditary cancer counseling.
- ONT-LRS represents a valuable tool for comprehensive genomic profiling in hereditary cancer syndromes.
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