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<p>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 <i>IDH1</i>/<i>IDH2</i> and <i>BRAF</i> 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 <i>CLIP2::MET</i> fusion as the sole pathogenic alteration. <i>MET</i> fusions are actionable oncogenic drivers across several cancers, and their detection has therapeutic relevance with approved inhibitors. This case expands the spectrum of <i>MET</i>-driven CNS tumors and suggests that <i>CLIP2::MET</i> fusion may represent a distinct molecular subset of glioneuronal tumors relevant to precision oncology.</p>

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CLIP2::MET fusion identifies a molecularly distinct glioneuronal tumor

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月17日

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  • Jawad Fares,
  • Jared T. Ahrendsen,
  • Harrshavasan T. Congivaram,
  • Lucas Santana-Santos,
  • Daniel Oyon,
  • Karan Dixit,
  • Mark W. Youngblood,
  • James P. Chandler

摘要

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.