Neuro-oncology最新文献

{"title":"The prognostic value of CDKN2A/CDKN2B hemizygous deletion in meningioma remains uncertain.","authors":"Junpeng Ma, Wei Chen, Yaqiang Hong, Dake Zhang, Liang Wang","doi":"10.1093/neuonc/noag158","DOIUrl":"10.1093/neuonc/noag158","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2514-2515"},"PeriodicalIF":13.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to: Investigator-led clinical trial of boron neutron capture therapy system for recurrent high-grade meningiomas after radiation therapy: Randomized phase II study.","authors":"","doi":"10.1093/neuonc/noag230","DOIUrl":"https://doi.org/10.1093/neuonc/noag230","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SNP rs2853669 potentially elevates the risk of glioblastoma development and leads to worse prognosis when in cis with mutant TERT promoter in a Japanese cohort.","authors":"Daisuke Kawauchi, Yohei Miyake, Brett Taylor, Joseph Bendik, Shunichiro Miki, Mai Honda-Kitahara, Jill Barnholtz-Sloan, Tomoyuki Nakano, Philip Pham, Raghavendra Vadla, Brandon M Jones, Clark Wang, Sejal Patel, Yoshitaka Narita, Frank Furnari","doi":"10.1093/neuonc/noag237","DOIUrl":"https://doi.org/10.1093/neuonc/noag237","url":null,"abstract":"<p><strong>Background: </strong>Mutations in the telomerase reverse transcriptase (TERT) promoter region (TPM), particularly C228T and C250T, are common in IDH-wildtype glioblastoma (GBM). The single nucleotide polymorphism (SNP) rs2853669, also located in the TERT promoter, may influence telomerase activity, though its clinical relevance in GBM remains unclear. This study examined the allelic configuration between rs2853669 and TPM to elucidate their combined effects on TERT expression and clinical outcome.</p><p><strong>Methods: </strong>Seventy-six TPM-positive GBM tumors from Japanese patients were analyzed by nested PCR, and patients were classified by rs2853669 genotype (T/T, T/C, C/C). In the T/C subgroup, the allelic configuration between the SNP and TPM was determined as cis (same allele) or trans (different alleles). Clinical data, TERT expression, and prognosis were compared among groups.</p><p><strong>Results: </strong>Among 76 patients, 37 (48.7%) had T/T, 30 (39.5%) had T/C, and 9 (11.8%) had C/C genotypes. The rs2853669 C allele frequency was higher in GBM than in the general Japanese population (31.6% vs 24.5%, p = 0.047). Among T/C cases, 53.3% showed a cis configuration. Patients carrying the SNP and TPM on the same allele (C/C and T/C cis) had shorter overall survival than those carrying them on different alleles (T/T or T/C trans; 19 vs 25 months, p = 0.048), and TERT expression was also lower in this group (p = 0.038).</p><p><strong>Conclusion: </strong>The rs2853669 C allele may increase GBM susceptibility and, when in cis with TPM, is associated with reduced TERT expression and poorer prognosis, underscoring its biological and clinical significance in TPM-mutant GBM.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"H3K27me3 loss and METTL3-m6A converge to upregulate SOX11/SMARCA4 and drive H3K27-altered spinal cord glioma stemness and proliferation.","authors":"Hao Yan, Jialin Jin, Yuzhou Chang, Bo Pang, Han Lin, Songyuan An, Lanhui Zheng, Yun Liu, Yilin Wu, Wenhao Xia, Bing Sun, Yantao Liu, Xiaoyang Qin, Wenqing Jia, Ruichao Chai, Yongzhi Wang","doi":"10.1093/neuonc/noag232","DOIUrl":"https://doi.org/10.1093/neuonc/noag232","url":null,"abstract":"<p><strong>Background: </strong>H3 K27-altered diffuse midline gliomas (H3-DMGs) are driven by stem-like and proliferative tumor cells resulting from global H3K27me3 loss. Here, we aimed to identify key molecular mechanisms involved in the interplay between epigenetic and epitranscriptomic regulation underlying this process.</p><p><strong>Methods: </strong>Patient-derived spinal cord H3-DMG stem-like spheres and serum-induced differentiated cells were used to model tumor plasticity. Multi-omics approaches, including single-cell RNA sequencing, spatial transcriptomics, RNA m6A profiling, CUT&Tag, ATAC-seq, and in vitro and in vivo assays were performed to dissect epigenetic and epitranscriptomic regulation of stemness.</p><p><strong>Results: </strong>Differentiation reduced stemness markers, proliferation, H3K27M expression, and global m6A levels, while increasing H3K27me3. METTL3 was significantly downregulated during differentiation and positively correlated with stemness and proliferation in patient tumors. METTL3 promoted tumor stemness and growth by stabilizing SOX11 mRNA through YTHDC2-dependent m6A recognition. In parallel, H3K27me3 loss relieved transcriptional repression at both METTL3 and SOX11 loci, leading to SOX11 overexpression. Functionally, SOX11 interacted with SMARCA4, the core ATPase of the SWI/SNF complex, to enhance chromatin accessibility and activate stemness-associated transcriptional programs marked by H3K27ac and H3K4me3 enrichment. Clinically, METTL3 and SOX11 were upregulated in H3K27M-mutant tumors, and high SOX11 expression correlated with increased proliferation, poor prognosis, and enhanced sensitivity to the SMARCA4 inhibitor BRM014.</p><p><strong>Conclusions: </strong>H3K27M-driven epigenetic dysregulation promotes SOX11 overexpression through combined H3K27me3 loss and METTL3-mediated m6A modification. SOX11 sustains tumor stemness and proliferation by recruiting SMARCA4 to remodel chromatin and serves as both a prognostic biomarker and a predictor of response to SMARCA4-targeted therapy in spinal cord H3-DMG.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"All roads lead to ROAM: A look at the results of the ROAM/EORTC-1308 clinical trial.","authors":"Felix Ehret, David R Raleigh","doi":"10.1093/neuonc/noag234","DOIUrl":"https://doi.org/10.1093/neuonc/noag234","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of high tumor mutational burden with brain metastases: Insights from a large-scale database analysis.","authors":"Marana Abboud, Saumya Sisoudiya, Benjamin Kaplan, Tomer Elisha, Laureen Goodman, Fayhaa Khair, Smruthy Sivakumar, Ethan Sokol, Ido Wolf, Tami Rubinek","doi":"10.1093/neuonc/noag222","DOIUrl":"https://doi.org/10.1093/neuonc/noag222","url":null,"abstract":"<p><strong>Background: </strong>Brain metastases (BrM) are a major cause of cancer-related mortality. To successfully colonize the brain, cancer cells must acquire unique adaptations. We hypothesized that BrM, regardless of their primary tumor origin, share convergent molecular features enabling brain colonization while retaining tumor type-specific alterations.</p><p><strong>Methods: </strong>We analyzed genomic data from 150,486 tumor samples, including BrM (N = 4,538), non-brain metastases (non-BrM, N = 43,844), and local biopsies (LB, N = 71,738) across six cancer types: non-small cell lung cancer (NSCLC), colorectal cancer (CRC), breast cancer (BC), esophageal cancer, melanoma, and neuroendocrine tumors (NET). We compared genomic alterations (GA), pathway enrichment, high tumor mutation burden (TMB-high), and high microsatellite instability (MSI-H) across groups.</p><p><strong>Results: </strong>Our research revealed that BrM were enriched for TMB-high and exhibited higher median values across all cancer types studied, compared to both LB and non-BrM. Interestingly, MSI-H, despite its known association with TMB-high, was not significantly enriched in BrM. We further showed a consistent enrichment of GA in TP53 in BrM across multiple tumor types. KRAS mutations were enriched in NSCLC and CRC BrM, while GA in TERT were specific to melanoma BrM. Pathway analysis showed that BrM have a higher frequency of GA in genes associated with the ERK-MAPK pathway and, to a lesser extent, the DNA damage response pathway.</p><p><strong>Conclusions: </strong>BrM harbor both tumor-specific and shared molecular traits, particularly TMB-high and recurrent TP53/KRAS alterations, potentially reflecting essential adaptations for BrM. These insights provide a molecular framework for developing targeted therapeutic strategies to prevent or treat BrM.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem cell morphology defines functional heterogeneity and therapeutic vulnerabilities in glioblastoma.","authors":"Carlotta Barelli, Matteo Bonfanti, Filippo Mirabella, Dario Ricca, Negin Alizadehmohajer, Roberta Bosotti, Ilaria Bertani, Viktoria Sokolova, Alberto Campione, Giovanni M Sicuri, Clelia Peano, Stefania Faletti, Roberto Stefini, Nereo Kalebic","doi":"10.1093/neuonc/noag235","DOIUrl":"https://doi.org/10.1093/neuonc/noag235","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) is an aggressive brain tumor and an unmet clinical need due to its invasiveness and therapy resistance. These features are driven by glioblastoma stem-like cells (GSLCs), which exhibit remarkable functional heterogeneity. While transcriptional profiling has helped define this heterogeneity, it alone does not fully predict cellular behaviors. Because cell morphology is closely linked to function during neurodevelopment, we asked whether integrating morphological and transcriptomic identities could reveal clinically relevant roles of GSLCs.</p><p><strong>Methods: </strong>We employed CellShape-seq, a customised spatial transcriptomics platform integrating cell morphology with transcriptome and applied it to patient-derived GBM organoids. To link GSLC transcriptome to function, we combined assembloid invasion assays, calcium imaging, pharmacological perturbations and time-lapse microscopy.</p><p><strong>Results: </strong>We identified three GSLC morphological classes corresponding to distinct transcriptomic states and functional behaviors: nonpolar cells, which show differentiation and therapy sensitivity; elongated cells, which are blood-vessel associated, invasive and chemoresistant; and multipolar cells, which form intercellular networks conveying therapy resistance. Importantly, morphological state remains stable throughout interphase and is readily inherited from mother to daughter cells. However, under pharmacological stress GSLCs show striking morphological plasticity. Namely, Temozolomide treatment is associated with GSLC elongation and branching, while YAP inhibition and gap-junction blockage result in a reduction of elongated and multipolar GSLCs, respectively. Finally, combined targeting of these morphoclass-specific vulnerabilities reduces viability in patient-derived organoids.</p><p><strong>Conclusion: </strong>Our findings demonstrate that cell morphology provides critical insights into GSLC behaviors and establish a rationale for putative morphology-informed therapies to overcome resistance and improve outcomes in GBM.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer Neuroscience: Establishing a home in Neuro-Oncology.","authors":"Shawn L Hervey-Jumper, Michelle Monje, Frank Winkler, David H Gutmann","doi":"10.1093/neuonc/noag129","DOIUrl":"https://doi.org/10.1093/neuonc/noag129","url":null,"abstract":"<p><p>Although neurons innervate all organs in which solid tumors grow, the role of neurons in cancer biology has long been neglected. Over the past decade, numerous studies have elucidated the critical role of the nervous system in cancer pathophysiology, culminating in the birth of Cancer Neuroscience. The recognition that neurons dictate many aspects of tumor biology not only provides new opportunities for therapeutic targeting of these stromal dependencies but also underscores the strong bi-directional relationships between tumors and the nervous system that result in cancer-associated symptomatology. By recognizing the key place of neurons in tumor biology, Cancer Neuroscience has ushered in a new era in which brain cancers should be conceptualized as diseases of dysregulated neurodevelopment, neuroplasticity, and neurophysiological function, usurped to drive brain cancer growth, progression, and therapeutic resistance. Likewise, the nervous system governs the initiation, growth, spread, and survival of most (if not all) extracranial cancers, while also mediating communication from cancers to the brain. Herein, we outline the current state of Cancer Neuroscience and the roles for neuro-oncologists in this new aspect of cancer care as an introduction to an upcoming series of articles in Neuro-Oncology on cellular interactions in the healthy nervous system and in the setting of cancer.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glioma and ependymoma through the lens of brain development, stem cells, and plasticity.","authors":"Costanza Lo Cascio, Antoni Martija, Mariella G Filbin, Aparna Bhaduri","doi":"10.1093/neuonc/noag200","DOIUrl":"https://doi.org/10.1093/neuonc/noag200","url":null,"abstract":"<p><p>Brain tumors are increasingly understood as having components of a development organization in which malignant cells leverage neural progenitor programs, lineage hierarchies, and circuit interactions that normally shape the developing brain. This review examines how these principles inform the biology of ependymoma and gliomas across the age spectrum, including H3 K27-altered diffuse midline glioma, H3 G34-mutant diffuse hemispheric glioma, IDH-mutant glioma, and glioblastoma. We highlight how tumor identity reflects developmental timing, regional context, and cell-of-origin competence, while also emphasizing that malignant cells can acquire plasticity beyond their normal counterparts. Across entities, single-cell, spatial, lineage-tracing, and organoid studies reveal progenitor-like compartments that sustain tumor growth, generate heterogeneous malignant states, and interact dynamically with the neural and immune microenvironment. Cancer neuroscience further extends this developmental framework by showing that neuronal activity, synaptic input, and neuromodulatory signaling can regulate tumor proliferation, migration, epigenetic state, and therapeutic response. Together, these findings argue that brain tumors should be viewed not as disorganized cellular masses but as aberrant developmental systems. Defining the developmental dependencies and circuit vulnerabilities of malignant progenitor states may enable more precise therapies that target tumor biology while preserving essential brain function.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of [18F]FET-PET on MRI-Based Radiotherapy Target Volumes in Newly Diagnosed Glioblastoma:Results from the FET-PET in Glioblastoma (FIG) Study TROG 18.06.","authors":"E-S Koh, R J Francis, G Ninatti, I Ruisi, M A Ebert, E Lau, A Whitehead, J Descallar, E H Barnes, S T Lee, E L Thomas, M B Pinkham, M Back, S P Ng, N Bucknell, H K Gan, O Cook, R Dykyj, A Moore, S Porter, Patricia Banyer, F E Scott, D L Bailey, N Barry, T Akhurst, R Alipour, A Bece, C Bettingdon, S Beuzeville, J H Chang, B Chua, C Clark, J Croker, S Gill, P Gorayski, E Hsiao, K Jung, S Khan, D Krishna, I Kirkwood, H Le, P Lin, T Ly, M McGuiness, S Ngai, D A Pattison, C Phillips, A P Pullar, G Schembri, J Sia, F Syed, P Thomas, W Vallat, M Wada, D Wong, J Yap, T C Yeow, A K Nowak, F Foroudi, M Rosenthal, P Roach, L Adda, R De Abreu Lourenco, B A Moffat, C Brighi, A Lasocki, L Holloway, M Fay, A M Scott","doi":"10.1093/neuonc/noag229","DOIUrl":"https://doi.org/10.1093/neuonc/noag229","url":null,"abstract":"<p><strong>Background: </strong>The FET-PET in Glioblastoma (FIG) study (TROG 18.06) assessed the impact of adding FET-PET to MRI on radiotherapy gross tumor volume delineation in newly diagnosed glioblastoma.</p><p><strong>Methods: </strong>This multicenter prospective phase 2 study evaluated participants with newly diagnosed glioblastoma IDH-wildtype undergoing post-operative MRI and FET-PET imaging before adjuvant radiotherapy, delivered according to standard MRI-based planning. The FET-PET-positive biological tumor volume (BTV) was used to derive the Hybrid (FET-PET+MRI) gross tumor volume (Hybrid-GTV). Primary outcomes were: 1) BTV excluded from the GTV defined on MRI alone (MR-GTV); 2) Hybrid-GTV excluded from the MR-GTV with both comparisons analyzed by non-overlap volume (cm3 and %), dosimetry (D98 and V95) and spatial similarity metrics; 3) clinically meaningful change in GTV non-overlap percentage volume with the addition of FET-PET.</p><p><strong>Results: </strong>There were 172 participants recruited, n = 140 evaluable. Median BTV was 23.1 cm3, median MR-GTV was 32.1 cm3, and median Hybrid-GTV was 46.0 cm3. Hybrid-GTV was significantly larger than the MR-GTV (p < 0.001), with a larger Hybrid-GTV observed in 83% of cases. Comparing BTV to MR-GTV, median non-overlap volume was 10.1 cm3 and non-overlap percentage volume 53.5%. Comparing Hybrid-GTV to MR-GTV, median non-overlap volume was 14.9 cm3 and non-overlap percentage volume 33.9%. D98 and V95 were lower for the Hybrid-GTV than for the MR-GTV, suggesting lower dose coverage. Applying a > 20% non-overlap percentage volume threshold, 76% of participants had a meaningful change in GTV with the addition of FET-PET.</p><p><strong>Conclusion: </strong>FET-PET differed significantly from MRI-based GTV delineation, with its incorporation leading to a clinically meaningful change in GTV in the majority of participants.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}