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Updated: Oct 18, 2025

Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
Catalog of 5' fusion partners in RET+ NSCLC Circa 2020
Sai-Hong Ignatius Ou1, Viola W Zhu1
1Chao Family Comprehensive Cancer Center, Department of Medicine, Division of Hematology and Oncology, University of California Irvine School of Medicine, Orange, California.
Abstract:
Since the discovery of RET fusion-positive (RET+) NSCLC around late 2011 to early 2012, clinical trials of multikinase inhibitors and highly potent and selective RET tyrosine kinase inhibitors have indicated that RET fusion is an actionable oncogenic driver in NSCLC. There seems to be a differential response to multikinase inhibitors depending on the fusion partner (KIF5B-RET versus non-KIF5B-RET); thus, knowledge of the fusion partners in RET+ NSCLC is important. To date, we identified 48 unique fusion partners in RET from published literature and congress proceedings. Two of the novel fusion partners (CCNYL2 and TRIM24) were identified in RET fusions that emerged as resistant to EGFR tyrosine kinase inhibitors. In addition, multiple intergenic rearrangements were identified.
Insights
Researchers identified 48 RET fusion partners in non-small cell lung cancer (NSCLC), including novel ones conferring resistance to EGFR inhibitors. Understanding these fusions is crucial for targeted therapy in RET-positive NSCLC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- RET fusions are actionable oncogenic drivers in non-small cell lung cancer (NSCLC).
- Differential responses to therapies exist based on RET fusion partners (e.g., KIF5B-RET vs. non-KIF5B-RET).
- Identifying fusion partners is critical for effective treatment strategies in RET-positive NSCLC.
Purpose of the Study:
- To comprehensively identify and characterize fusion partners involving the RET gene in NSCLC.
- To investigate novel RET fusion partners, particularly those associated with therapeutic resistance.
Main Methods:
- Systematic review and analysis of published literature and congress proceedings.
- Identification of unique RET fusion partners and intergenic rearrangements.
Main Results:
- Identified 48 unique fusion partners for RET in NSCLC.
- Discovered two novel fusion partners, CCNYL2 and TRIM24, in RET fusions.
- These novel fusions were associated with resistance to EGFR tyrosine kinase inhibitors.
Conclusions:
- The study expands the known landscape of RET fusions in NSCLC.
- Novel RET fusion partners can confer resistance to existing targeted therapies.
- Characterization of RET fusion partners is essential for developing next-generation therapies for NSCLC.
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07:59Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
10:35A Blood-based Test for the Detection of ROS1 and RET Fusion Transcripts from Circulating Ribonucleic Acid Using Digital Polymerase Chain Reaction
Published on: April 5, 2018
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