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Updated: Jun 19, 2026
Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
CLIP2::MET fusion identifies a molecularly distinct glioneuronal tumor
Jawad Fares1,2, Jared T Ahrendsen3, Harrshavasan T Congivaram4,5
1Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, 606011, USA. jawad.fares@northwestern.edu.
Abstract:
Glioneuronal tumors are rare central nervous system (CNS) neoplasms with heterogeneous clinical, histological, and molecular features. Diagnosis and classification are often challenging due to overlapping morphology and limited defining alterations. Here, we present a 19-year-old female with a right frontal lobe glioneuronal tumor, initially suspected to be a low-grade glioma. Histology revealed mixed glial and neuronal elements with low proliferative activity. Standard molecular testing was negative for IDH1/IDH2 and BRAF mutations. DNA methylation profiling did not match to any known CNS class but clustered most closely with low-grade glioma/ganglioglioma. Next-generation RNA sequencing identified a CLIP2::MET fusion as the sole pathogenic alteration. MET fusions are actionable oncogenic drivers across several cancers, and their detection has therapeutic relevance with approved inhibitors. This case expands the spectrum of MET-driven CNS tumors and suggests that CLIP2::MET fusion may represent a distinct molecular subset of glioneuronal tumors relevant to precision oncology.
Insights
A rare glioneuronal tumor in a young female was identified with a novel CLIP2::MET fusion. This finding expands the understanding of MET-driven central nervous system (CNS) tumors and offers potential therapeutic targets.
Area of Science:
- Neuro-oncology
- Molecular Pathology
- Genomics
Background:
- Glioneuronal tumors are rare central nervous system (CNS) neoplasms with challenging diagnoses due to heterogeneous features.
- Limited defining molecular alterations complicate classification and treatment strategies for these tumors.
Purpose of the Study:
- To characterize the molecular underpinnings of a glioneuronal tumor in a 19-year-old female.
- To identify novel oncogenic drivers for potential targeted therapies in CNS tumors.
Main Methods:
- Histopathological examination of tumor tissue.
- Standard molecular testing for IDH1/IDH2 and BRAF mutations.
- DNA methylation profiling.
- Next-generation RNA sequencing.
Main Results:
- Histology showed a mixed glial and neuronal tumor with low proliferative activity.
- Standard molecular tests and DNA methylation profiling did not yield a definitive classification.
- Next-generation RNA sequencing identified a CLIP2::MET fusion as the sole pathogenic alteration.
Conclusions:
- The CLIP2::MET fusion represents a distinct molecular subset of glioneuronal tumors.
- MET fusions are actionable oncogenic drivers with therapeutic relevance in CNS oncology.
- This case highlights the importance of advanced molecular profiling for precision oncology in rare CNS neoplasms.
