Expanded Fusion Panel Helps Identify Potentially Significant Long Noncoding RNA and Other Novel Fusions Across Solid Tumor Types
Key Clinical Summary
- Population and Design: Retrospective analysis of 547 solid tumor FFPE specimens using a 153-gene targeted fusion panel identified gene rearrangements in 21.8% of cases.
- Findings: 18.5% of fusions were novel, and 4.2% involved long noncoding RNA (lncRNA) partners; recurrent partners included HMGA2, NRG1, EGFR, and NFIB. 18 new oncogenic rearrangements were confirmed across tumor types, including glioblastoma, liver, lung, bladder, breast, thyroid, bile duct, skull, and fibrosarcoma.
- Clinical Relevance: Detection of lncRNA and rare fusion events provides diagnostic insights in difficult-to-classify tumors and may hold future therapeutic significance, warranting further molecular investigation.
A retrospective analysis using a 153-gene targeted fusion panel identified novel gene fusions, including long noncoding RNA (lncRNA) fusion partners, across multiple solid tumor types, according to study results from the 2025 Association for Molecular Pathology Annual Meeting & Expo.
Previous research has identified tumor-specific lncRNA fusions which may influence gene regulation. Researchers conducted a retrospective analysis to identify lncRNA and other novel fusions in solid tumors, to determine if their networks play a role in gene regulation, exploring them as potential targets for diagnosis and therapy.
Among 547 formalin-fixed, paraffin-embedded (FFPE) tumor specimens tested, gene rearrangements were detected in 21.8% of cases. Of these, 18.5% harbored fusions not previously reported in the literature or fusion databases and 4.2% involved lncRNAs as partner genes. Partner genes were identified were HMGA2 (n=2), NRG1, EGFR, and NFIB.
In addition to lncRNA fusions, 18 novel oncogenic rearrangements were identified in 17 tumor specimens, spanning a range of tumor types which included:
- Glioblastoma: IFNAR1::ERG, R3HDM2::GLI1,
- Liver: CLIPTM1L::TERT, SMG1::MUSK, ARHGEF7::NTRK3, PAX3::COL6A3,
- Lung: ATXN10::ERG, NKD1::ERG, CRTC1::CYP4F11, GRIA4::PDGFD,
- Bladder: MEAF6::RIMS3, MDM2::OSBPL,
- Breast: SLC12A7::TERT, UQCRH::MAST2,
- Other Sites: PHLPP1::SS18 (bile duct), MEAF6::GMEB1 (thyroid), FN1::PDGFRB (skull), MPRIP::BRAF (fibrosarcoma).
All novel fusion findings were confirmed through reverse transcription PCR and Sanger sequencing. One fusion was additionally validated by an external reference lab.
The researchers concluded, “Expanded fusion panels helped identify new, clinically important gene fusions. Some novel fusions contributed to diagnosis, prognosis, and may have value in patient management. Notably, the detection of lncRNA fusions, an area of growing interest, provided insights in diagnostically challenging cases.”
They added, “Although lncRNA fusions are currently considered as fusions of unknown significance, they may have potential clinical implications and warrant further investigation.”
Source:
Guseva N, Parida M, Hornberg S, et al. Detection of Long Non-Coding RNA and Other Novel Gene Fusions in Solid Tumors Using a Custom-Designed Expanded FUSIONplex Assay. Presented at the 2025 AMP Annual Meeting. November 11-15, 2025; Boston, Massachusetts. ST080
