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Updated: Oct 4, 2025
Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
A functional genomic approach to actionable gene fusions for precision oncology
Jun Li1, Hengyu Lu2, Patrick Kwok-Shing Ng3
1Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Abstract:
Fusion genes represent a class of attractive therapeutic targets. Thousands of fusion genes have been identified in patients with cancer, but the functional consequences and therapeutic implications of most of these remain largely unknown. Here, we develop a functional genomic approach that consists of efficient fusion reconstruction and sensitive cell viability and drug response assays. Applying this approach, we characterize ~100 fusion genes detected in patient samples of The Cancer Genome Atlas, revealing a notable fraction of low-frequency fusions with activating effects on tumor growth. Focusing on those in the RTK-RAS pathway, we identify a number of activating fusions that can markedly affect sensitivity to relevant drugs. Last, we propose an integrated, level-of-evidence classification system to prioritize gene fusions systematically. Our study reiterates the urgent clinical need to incorporate similar functional genomic approaches to characterize gene fusions, thereby maximizing the utility of gene fusions for precision oncology.
Insights
Researchers developed a functional genomic method to analyze cancer fusion genes. This approach identified novel fusion genes that drive tumor growth and impact drug sensitivity, aiding precision oncology efforts.
Area of Science:
- Genomics
- Cancer Biology
- Drug Discovery
Background:
- Fusion genes are key targets in cancer therapy, but their functions are often unknown.
- Thousands of cancer-associated fusion genes have been identified, necessitating functional characterization.
- Understanding fusion gene implications is crucial for advancing precision oncology.
Purpose of the Study:
- To develop and apply a functional genomic approach for characterizing cancer fusion genes.
- To identify novel fusion genes with functional roles in tumor growth and drug response.
- To establish a system for prioritizing fusion genes for therapeutic development.
Main Methods:
- Efficient reconstruction of fusion genes.
- Sensitive cell viability and drug response assays.
- Analysis of approximately 100 fusion genes from The Cancer Genome Atlas (TCGA).
Main Results:
- Identified a significant number of low-frequency fusion genes with tumor growth-activating effects.
- Discovered activating fusion genes within the RTK-RAS pathway that alter drug sensitivity.
- Demonstrated the utility of functional genomics in uncovering fusion gene functions.
Conclusions:
- Functional genomic characterization is essential for understanding fusion gene roles in cancer.
- This approach can identify actionable fusion targets for precision oncology.
- A systematic classification system can prioritize fusion genes for clinical investigation.
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