{"doi":"10.1093/noajnl/vdaf197","title":"<i>H3K27M-</i> and <i>BRAF V600E</i> -Altered gliomas and glioneuronal tumors—clinico-pathologic and radiologic perspective in a cohort treated with targeted therapy","abstract":"AbstractAbstract Background Among diffuse midline gliomas with H3K27-altered with MAPK pathway mutations, those with BRAF V600E mutations show the most histologic variability and potential for targeted therapy, yet remain incompletely characterized. We present a series of such tumors, focusing on imaging, histologic, molecular, and therapeutic features. Methods Pathology archives from 2016 to 2025 at our institution were searched for gliomas with H3K27M/BRAF V600E mutations. Clinical history, imaging, histology, molecular findings, therapy, and outcomes were reviewed. Results Eight patients were identified (6 males, 2 females; age 3-18 years, average 11). Six tumors were thalamic, one cervical, and one suprasellar. Histology fell into three categories: low-grade glioma-like (n = 3), ganglioglioma-like (n = 3), and high-grade glioma-like (n = 2). Tumors with low-grade morphology had no additional clinically significant mutations, while high-grade tumors had co-occurring variants including TERT, 1q/5q gains, and polysomy 7. Two tumors had no methylation class match; two clustered with diffuse midline glioma, and one clustered with high-grade glioma with piloid features. Six patients had maximal safe resections, and two had biopsies (1 low-grade, 1 high-grade). All received BRAF/MEK inhibitors; six also had radiation, and two had chemotherapy. The two patients with high-grade tumors had outcomes similar to classic H3K27M diffuse midline gliomas (both deceased at 17 and 12 months). Patients with low-grade glioma or ganglioglioma-like tumors had better outcomes (all alive, average 38-month follow-up, range 6-80 months). Conclusion H3K27M/BRAF V600E-mutant gliomas may represent a distinct subgroup, with outcomes linked to histologic and co-occurring molecular features. Targeted therapy and a surgical approach may support long-term survival in low-grade cases.","journal":"Neuro-Oncology Advances","year":2025,"id":574387,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9463,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1053960,"name":"Vanessa Rameh","orcid":"0000-0002-6007-7216","position":1,"is_corresponding":false},{"id":1481781,"name":"Tom Rosenberg","orcid":"0000-0002-9592-2539","position":2,"is_corresponding":false},{"id":627806,"name":"Kee Kiat Yeo","orcid":"0000-0003-0713-6384","position":3,"is_corresponding":false},{"id":18802,"name":"Susan Chi","orcid":"0000-0001-7753-878X","position":4,"is_corresponding":false},{"id":18801,"name":"Karen Wright","orcid":"0000-0002-9578-1545","position":5,"is_corresponding":false},{"id":236609,"name":"Lissa Baird","orcid":"0000-0001-7996-1020","position":6,"is_corresponding":false},{"id":1375291,"name":"Mariella G Filbin","orcid":null,"position":7,"is_corresponding":false},{"id":1057268,"name":"Katie Fehnel","orcid":"0000-0001-9701-0931","position":8,"is_corresponding":false},{"id":240507,"name":"Zied Abdullaev","orcid":"0000-0001-6345-2088","position":9,"is_corresponding":false},{"id":13200,"name":"Kenneth Aldape","orcid":"0000-0001-5119-7550","position":10,"is_corresponding":false},{"id":568650,"name":"Hart G.W. Lidov","orcid":"0000-0002-1839-7603","position":11,"is_corresponding":false},{"id":25330,"name":"Sanda Alexandrescu","orcid":"0000-0001-9246-4184","position":12,"is_corresponding":false},{"id":968254,"name":"Carolyn G Chen","orcid":null,"position":0,"is_corresponding":true}],"reference_count":16,"raw_metadata":null,"created_at":"2026-07-19T02:57:40.686992Z","pmid":"41473746","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}