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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 (<jats:italic>EGFR<\/jats:italic>) and vesicular, overexpressed in cancer, prosurvival protein 1 (<jats:italic>VOPP1)<\/jats:italic> 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 (NF\u03baB) 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.<\/jats:p>","DOI":"10.1186\/s40478-025-01994-1","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T02:42:28Z","timestamp":1744771348000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["VOPP1::EGFR fusion is associated with NF\u03baB pathway activation in a glioneural tumor with histological features of ganglioglioma"],"prefix":"10.1186","volume":"13","author":[{"given":"Max","family":"Braune","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathias","family":"Stiller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cordula","family":"Scherlach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Wilhelmy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katja","family":"J\u00e4hne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolf C.","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alonso","family":"Barrantes-Freer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,4,16]]},"reference":[{"key":"1994_CR1","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1093\/jnen\/61.7.575","volume":"61","author":"I Blumcke","year":"2002","unstructured":"Blumcke I, Wiestler OD (2002) Gangliogliomas: an intriguing tumor entity associated with focal epilepsies. 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The report is based on surgically removed tissue in the context of routine diagnostic workup and represent a retrospective observational study of a single case. Therefore, the Ethics Committee of the medical faculty of the university medical center Leipzig (UKL) has confirmed that no ethical approval is required as regulated by paragraph 15 of the professional regulation of the medical association of Saxony, Germany (\u00a7\u00a015 BO, SL\u00c4K). Consent for scientific usage of tumor tissue and publishing of respective data was obtained from the patient.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The patient has given explicit written consent for scientific usage and publication of clinical, radiological and neuropathological data.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"76"}}