ArticleJCO precision oncology2025
Clinical Implementation of Expanded Solid Tumor Fusion Detection With Whole-Transcriptome Sequencing at an Academic Cancer Center.
Article in JCO precision oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Development and validation of an interpretable prediction model using spatial patterns of tumor-infiltrating lymphocytes in H&E-stained whole-slide images for immune subtyping of lung adenocarcinoma.Frontiers in immunology · 2026Article
- Reference-free RNA profiling predicts triple negative breast cancer chemoresistance to neoadjuvant treatment.NAR cancer · 2025Article
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14 authors.
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Abstract
purposeChromosomal rearrangements drive tumorigenesis through fusion transcripts. Clinical whole-transcriptome sequencing (WTS) enables comprehensive fusion detection, overcoming limitations of targeted methods, but its clinical application has been hindered by technical and cost barriers.
methodsWe validated a clinical bait-capture WTS assay using 78 solid tumor samples across diverse tissue types, including 59 with known fusions or oncogenic splice variants. Sensitivity was assessed against clinically reported fusions from targeted next-generation sequencing or fluorescence in situ hybridization. Analytical performance was evaluated for sensitivity, specificity, limit of detection, and reproducibility across varying RNA inputs and sequencing conditions. Clinical implementation data were also analyzed.
resultsWTS demonstrated a sensitivity of 97.1% and a specificity of 100% for detecting clinically relevant fusions. Detection was robust across tumor types, with RNA input as low as 1 ng. Optimized sequencing thresholds of 60 million reads and 130-bp read length improved performance. The assay was highly reproducible and resistant to common contaminants. Over 6 months of clinical use (410 specimens), WTS identified 29 fusions (7% detection rate), including six clinically relevant fusions undetectable by our institution's previous targeted panel, increasing the fusion yield by 26%.
conclusionWTS provides high sensitivity, specificity, and expanded fusion detection, supporting its routine clinical adoption. Future work will explore its broader role in integrated genomic profiling and therapeutic guidance.
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