# VOPP1::EGFR fusion is associated with NFκB pathway activation in a glioneural tumor with histological features of ganglioglioma

## TL;DR

A new gene fusion involving EGFR and VOPP1 is linked to tumor growth in a brain tumor resembling ganglioglioma, offering potential treatment targets.

## Contribution

First report of the VOPP1::EGFR fusion as an oncogenic driver in a glioneuronal tumor resembling ganglioglioma.

## Key findings

- VOPP1::EGFR fusion activates the NFκB signaling pathway in the tumor.
- The tumor exhibits histological and epigenetic features consistent with ganglioglioma.
- The case expands the molecular understanding of oncogenic drivers in glioneuronal tumors.

## Abstract

Glioneural tumors are primary brain tumors that consist of both neural and glial neoplastic cells, often presenting with seizures and primarily affecting children and young adults. Specifically, gangliogliomas are composed of neoplastic ganglion and glial cells, accompanied by other characteristic histological features such as lymphoid cuffing, eosinophilic granular bodies, and Rosenthal fibers. Oncogenic driver mutations and gene fusions have been shown to be of prognostic significance in gangliogliomas and can offer potential therapeutic targets. Typical molecular alterations are mitogen-activated protein kinase (MAPK) pathway activations with BRAF p.V600E being the most frequent one. Here, we report for the first time a gene fusion between epidermal growth factor receptor (EGFR) and vesicular, overexpressed in cancer, prosurvival protein 1 (VOPP1) as a potential oncogenic driver in a glioneuronal tumor morphologically resembling ganglioglioma. VOPP1::EGFR fusion associated with the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) signaling. Furthermore, we provide histological and epigenetic findings and clinical outcome. The case expands the known molecular spectrum of oncogenic drivers in glioneuronal tumors and provides a link to potentially prognostic and therapeutically relevant alterations.

The online version contains supplementary material available at 10.1186/s40478-025-01994-1.