| Target/Gene | Alteration Type | Frequency in tumor subtype | Associated tumor subtype(s) | Targeted therapy options | ESCAT classification / guideline status | Clinical trial evidence (NCT) |
|---|---|---|---|---|---|---|
| **BRAF** | **p.V600E missense hotspot** | Ganglioglioma ~36.3–36.9%; DNET **<1/3** of cases; PLNTY subset; broader mixed neuronal-glial tumor association in OpenTargets (pqac-00000012, pqac-00000014, pqac-00000023, pqac-00000043, pqac-00000000) | Ganglioglioma, anaplastic ganglioglioma, DNET, PLNTY, other LEAT/glioneuronal tumors | **Dabrafenib + trametinib**; **vemurafenib**; other BRAF inhibitors; BRAF/MEK combination preferred for progressive/recurrent disease after standard care (pqac-00000018, pqac-00000020, pqac-00000031, pqac-00000037) | **Standard-of-care target in recurrent CNS tumors/glioneuronal tumors per EANO**; highest actionability among reviewed targets (pqac-00000031, pqac-00000033, pqac-00000037) | **NCT02684058** (dabrafenib + trametinib, pediatric BRAF V600 tumors); pediatric long-term follow-up **NCT03975829** |
| **BRAF** | **KIAA1549::BRAF fusion / other BRAF fusions** | Common in some low-grade glioma/glioneuronal contexts; reported in DLGNT and pilocytic-spectrum tumors; not a dominant alteration in classic ganglioglioma (pqac-00000011, pqac-00000029, pqac-00000035) | Diffuse leptomeningeal glioneuronal tumor (DLGNT), pilocytic-spectrum tumors, some mixed neuronal-glial tumors | **MEK inhibitors** or **type II RAF inhibitors** considered, preferably in trials for recurrent disease (pqac-00000037) | Therapeutically relevant in selected entities including **DLGNT**; EANO update notes growing relevance of fusion testing (pqac-00000035) | No subtype-specific dedicated trial identified here; may be captured in basket/brain tumor molecular trials |
| **FGFR1** | **Hotspot mutation (N546K, K656E), mutation/duplication/fusion spectrum** | **>75% in DNET** overall FGFR1-altered spectrum; only ~1.18% in ganglioglioma; in driver-unknown LGG/MNGT, FGFR1 N546/K656 mutations in **12%** (13/108) (pqac-00000023, pqac-00000011, pqac-00000012) | DNET, RGNT, some mixed neuronal-glial tumors, pilocytic-spectrum tumors | **FGFR inhibitors** (investigational; modest activity so far); molecular testing recommended when targeted options sought (pqac-00000031, pqac-00000038) | **ESCAT IIB** for FGFR alterations in glioneuronal tumors such as **RGNT/DNET** per EANO (pqac-00000038) | **NCT05267106** (pemigatinib in FGFR1-3 altered primary CNS tumors; terminated) |
| **NTRK1/2/3** | **Gene fusions** | Rare; OpenTargets supports NTRK3 association with mixed neuronal-glial tumor/ganglioglioma (pqac-00000000) | Rare glioneuronal tumors, mixed neuronal-glial tumors, ganglioglioma subset | **Larotrectinib**, **entrectinib** for fusion-positive recurrent disease, ideally in trials/registries (pqac-00000031, pqac-00000034, pqac-00000038) | **ESCAT IIB**; EANO recommends testing in patients who exhausted standard therapy and are fit for targeted treatment (pqac-00000031, pqac-00000032, pqac-00000038) | No mixed neuronal-glial subtype-specific NCT identified here; typically basket trial enrollment |
| **PRKCA** | **Fusion (especially SLC44A1::PRKCA)** | Characteristic / recurrent driver rather than population-frequency estimate provided (pqac-00000002, pqac-00000025, pqac-00000027) | Papillary glioneuronal tumor (PGNT) | No established approved matched therapy in current EANO guidance; primarily **diagnostic biomarker** | Not assigned as an actionable standard target in cited EANO therapeutic recommendations; clinical benefit not established (pqac-00000031) | No specific trial identified here |
| **PDGFRA** | **p.K385 mutation** | Defining recurrent alteration for myxoid glioneuronal tumor (MGT) (pqac-00000038, pqac-00000041, pqac-00000043) | Myxoid glioneuronal tumor | Currently mainly **diagnostic**; no standard targeted therapy established in cited guidance | Used as a **diagnostic marker** in EANO/WHO-era classification rather than validated therapeutic target (pqac-00000038, pqac-00000043) | No specific trial identified here |
| **H3-3A (H3F3A)** | **Histone H3 alterations (e.g., H3 K27M in rare cases)** | Rare in ganglioglioma (~0.74% in one systematic review context); OpenTargets association present (pqac-00000014, pqac-00000000) | Rare ganglioglioma/anaplastic ganglioglioma and mixed neuronal-glial tumors | No established targeted therapy in current glioneuronal standard care; investigational approaches only | Not a proven predictive target for routine targeted treatment in current EANO update (pqac-00000033) | No specific trial identified here |
| **PTEN** | **Loss / pathway alteration** | OpenTargets association present but no direct evidence count in cited dataset; may contribute to BRAFi resistance biology (pqac-00000000, pqac-00000020) | Mixed neuronal-glial tumor, resistant BRAF-mutant glioneuronal tumors | No established matched therapy in this disease context; relevant to resistance and PI3K/AKT/mTOR biology | Not validated as routine actionable target in current EANO guidance for glioneuronal tumors (pqac-00000033) | No specific trial identified here |
| **NF1 / KRAS / PTPN11 / other RAS-MAPK genes** | **Somatic mutation / CNV gain / pathway activation** | Defined adverse-outcome subgroup in ganglioglioma; exact subgroup small (8 PTPN11-altered GG in one series) (pqac-00000009, pqac-00000010, pqac-00000011) | Ganglioglioma with atypical histology/adverse seizure outcome; RGNT may carry NF1 co-alterations | No established approved subtype-specific therapy; **MAPK-pathway inhibitors** considered biologically relevant/investigational (pqac-00000010, pqac-00000017) | Not established as standard actionable targets; testing may be considered when trials/advanced molecular profiling are pursued (pqac-00000031, pqac-00000037) | **NCT04923126** (mirdametinib in low-grade glioma; includes MAPK-pathway disease context) |
| **PIK3CA / PIK3R1** | **Co-mutations / PI3K pathway activation** | Reported as co-alterations in RGNT and some glioneuronal tumors; no robust prevalence estimate here (pqac-00000002, pqac-00000029) | Rosette-forming glioneuronal tumor, some mixed neuronal-glial tumors | No established approved targeted therapy in this indication; pathway relevance mainly mechanistic | Not established as routine actionable target in current EANO recommendations for glioneuronal tumors (pqac-00000031, pqac-00000033) | No specific trial identified here |
| **ETV6** | **Fusion partner in NTRK3-related events / association in OpenTargets** | Rare; OpenTargets association only in current evidence set (pqac-00000000) | Rare mixed neuronal-glial tumors / ganglioglioma-related fusion-positive cases | If part of **ETV6::NTRK3**, therapy would follow **NTRK inhibitor** pathway (larotrectinib/entrectinib) | Follows **NTRK fusion** actionability rather than ETV6 alone (pqac-00000031, pqac-00000038) | Basket trial/registry approach; no specific subtype trial identified here |
| **IDH1** | **Mutation** | Rare / generally not characteristic; OpenTargets association exists but classic glioneuronal tumors are usually IDH-wildtype (pqac-00000000, pqac-00000014, pqac-00000023) | Rare atypical ganglioglioma or misclassified tumors | No established role in routine therapy for classic mixed neuronal-glial tumors | More relevant to differential diagnosis than to standard targeted treatment in this entity group (pqac-00000033) | No specific trial identified here |
| **MUTYH** | **Association only in OpenTargets** | No supporting evidence count in cited OpenTargets dataset (pqac-00000000) | Mixed neuronal-glial tumor | None established | No therapeutic actionability established | None identified |


*Table: This table summarizes the main molecular alterations linked to mixed neuronal-glial tumors and maps them to current or emerging targeted treatment options. It emphasizes where evidence is strongest—especially for BRAF V600E—and where alterations are primarily diagnostic rather than therapeutically validated.*