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Detecting Somatic Genetic Alterations in Tumor Specimens by Exon Capture and Massively Parallel Sequencing
Published on: October 18, 2013
Clinical Implementation of Expanded Solid Tumor Fusion Detection With Whole-Transcriptome Sequencing at an Academic
Edward G Hughes1, Drew T Bergman2,3, Donald C Green1
1Laboratory for Clinical Genomics and Advanced Technologies, Department of Pathology and Laboratory Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH.
JCO Precision Oncology
|May 29, 2025
Summary
Whole-transcriptome sequencing (WTS) offers a sensitive and specific method for detecting cancer-driving fusion transcripts. This validated clinical assay expands fusion detection beyond targeted panels, supporting its routine use in oncology.
Area of Science:
- Oncology
- Genomics
- Molecular Diagnostics
Background:
- Chromosomal rearrangements are key drivers of tumorigenesis, often resulting in fusion transcripts.
- Clinical whole-transcriptome sequencing (WTS) offers comprehensive fusion detection but faces technical and cost challenges.
- Targeted methods have limitations in detecting the full spectrum of fusion events.
Purpose of the Study:
- To validate a clinical bait-capture whole-transcriptome sequencing (WTS) assay for fusion transcript detection in solid tumors.
- To assess the analytical performance and clinical utility of WTS compared to existing methods.
- To evaluate the feasibility of routine clinical implementation of WTS for cancer diagnostics.
Main Methods:
- Validation of a clinical bait-capture WTS assay using 78 solid tumor samples.
- Assessment of sensitivity against clinically reported fusions detected by targeted next-generation sequencing or FISH.
- Evaluation of analytical performance including sensitivity, specificity, limit of detection, and reproducibility with varying RNA inputs.
Main Results:
- WTS achieved 97.1% sensitivity and 100% specificity for clinically relevant fusions.
- Robust detection was observed with as little as 1 ng of RNA input.
- Over 6 months, WTS identified 6 previously undetected clinically relevant fusions, increasing yield by 26%.
Conclusions:
- Validated WTS assay demonstrates high sensitivity, specificity, and expanded fusion detection capabilities.
- The findings support the routine clinical adoption of WTS for comprehensive genomic profiling in oncology.
- Future research will focus on integrating WTS into broader genomic profiling strategies for therapeutic guidance.
