Neuro-oncology最新文献

{"title":"DNA methylation profiling of pituitary neuroendocrine tumors identifies distinct clinical and pathological subtypes based on epigenetic differentiation.","authors":"Sarra Belakhoua, Varshini Vasudevaraja, Chanel Schroff, Kristyn Galbraith, Misha Movahed-Ezazi, Jonathan Serrano, Yiying Yang, Daniel Orringer, John G Golfinos, Chandra Sen, Donato Pacione, Nidhi Agrawal, Matija Snuderl","doi":"10.1093/neuonc/noaf109","DOIUrl":"10.1093/neuonc/noaf109","url":null,"abstract":"<p><strong>Background: </strong>Pituitary neuroendocrine tumors (PitNETs) are the most common intracranial neuroendocrine tumors. PitNETs can be challenging to classify, and current recommendations include a large immunohistochemical panel to differentiate among 14 WHO-recognized categories.</p><p><strong>Methods: </strong>In this study, we analyzed clinical, immunohistochemical, and DNA methylation data of 118 PitNETs to develop a clinicomolecular approach to classifying PitNETs and identifying epigenetic classes.</p><p><strong>Results: </strong>CNS DNA methylation classifier has an excellent performance in recognizing PitNETs and distinguishing the 3 lineages when the calibrated score is ≥ 0.3. Unsupervised DNA methylation analysis separated PitNETs into 2 major clusters. The first was composed of silent gonadotrophs, which form a biologically distinct group of PitNETs characterized by clinical silencing, weak hormonal expression on immunohistochemistry, and simple copy number profile. The second major cluster was composed of corticotrophs and Pit1 lineage PitNETs, which could be further classified using DNA methylation into distinct subclusters that corresponded to clinically functioning and silent tumors and are consistent with transcription factor expression. Analysis of promoter methylation patterns correlated with lineage for corticotrophs and Pit1 lineage subtypes. However, the gonadotrophic genes did not show a distinct promoter methylation pattern in gonadotroph tumors compared to other lineages. Promoter of the NR5A1 gene, which encodes SF1, was hypermethylated across all PitNETs clinical and molecular subtypes including gonadotrophs with strong SF1 protein expression indicating alternative epigenetic regulation.</p><p><strong>Conclusion: </strong>Our findings suggest that classification of PitNETs may benefit from DNA methylation for clinicopathological stratification.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2341-2354"},"PeriodicalIF":13.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12526055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013041","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":"A phase 2 PBTC study of selumetinib for recurrent/progressive pediatric low-grade glioma: Strata 2, 5, and 6 with long-term outcomes on strata 1, 3, and 4.","authors":"Jason Fangusaro, Arzu Onar-Thomas, Tina Young Poussaint, Shelly Lensing, Azra H Ligon, Neal Lindeman, Anuradha Banerjee, Lindsay B Kilburn, Alicia Lenzen, Natasha Pillay-Smiley, Ian F Pollack, Nathan J Robison, Sonia Partap, Ibrahim Qaddoumi, Daniel Landi, David T W Jones, Clinton F Stewart, Maryam Fouladi, Ira J Dunkel","doi":"10.1093/neuonc/noaf065","DOIUrl":"10.1093/neuonc/noaf065","url":null,"abstract":"<p><strong>Background: </strong>PBTC-029B was a phase 2 trial evaluating efficacy of selumetinib in children with recurrent/progressive low-grade glioma. We report results of strata 2, 5, and 6 with updated survivals for strata 1, 3, and 4.</p><p><strong>Methods: </strong>Stratum 2 included recurrent/progressive pilocytic astrocytoma (PA) not associated with neurofibromatosis type-1 (NF1) that screened negative for the BRAF-KIAA1549 fusion and BRAFV600E mutation. Stratum 5 enrolled non-PA that screened positive for one of the BRAF aberrations. Stratum 6 enrolled children who consented to tissue screening, but there was an assay failure. For long-term survivals, stratum 1 included non-NF1 PA positive for one of the BRAF aberrations; stratum 3 included NF1-associated pLGG; and stratum 4 included non-NF1 optic pathway/hypothalamic tumors.</p><p><strong>Results: </strong>Stratum 2: among 14 evaluable patients, there was 1 partial response (PR), 7 stable disease (SD), and 6 progressive disease (PD); the overall response rate (ORR) was 7.1%. Two-year progression-free survival (PFS)/overall survival (OS) were 57.1%/100%, respectively. Stratum 5: among 23 evaluable patients, there was 1 complete response (CR), 4 PR, 12 SD, and 6 PD; ORR was 21.7%. Two-year PFS/OS were 74.8%/100%, respectively. Stratum 6: among 26 evaluable patients, there were 7 PR, 14 SD, and 5 PD; ORR was 26.9%. Two-year PFS/OS were 72.0%/100%, respectively. The median follow-up for patients on strata 1, 3, and 4 without events are 60.4, 60.4, and 58.1 months, and 5-year PFS/OS were 30.8%/88.9%, 54.2%/100%, and 51.0%/100%, respectively.</p><p><strong>Conclusions: </strong>Selumetinib provided stability and responses across many pLGG subgroups, and some patients achieved prolonged disease control without additional therapy.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2415-2428"},"PeriodicalIF":13.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12526141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021096","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":"Point/Counterpoint: Intrathecal therapy for patients with leptomeningeal metastases from solid tumors.","authors":"Emilie Le Rhun, Barbara J O'Brien, Elena Pentsova, Matthias Preusser, Michael Weller, Adrienne Boire","doi":"10.1093/neuonc/noaf126","DOIUrl":"10.1093/neuonc/noaf126","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2225-2231"},"PeriodicalIF":13.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12526066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560641","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":"Unraveling the effects of radiotherapy on the blood-brain barrier: Fact or fiction?","authors":"Rupesh Kotecha, Minesh P Mehta","doi":"10.1093/neuonc/noaf137","DOIUrl":"10.1093/neuonc/noaf137","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2262-2264"},"PeriodicalIF":13.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12526051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187391","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":"CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2018-2022.","authors":"Mackenzie Price, Christine Ann Pittman Ballard, Julia R Benedetti, Carol Kruchko, Jill S Barnholtz-Sloan, Quinn T Ostrom","doi":"10.1093/neuonc/noaf194","DOIUrl":"10.1093/neuonc/noaf194","url":null,"abstract":"<p><p>The Central Brain Tumor Registry of the United States (CBTRUS), an aggregation of data from the Centers for Disease Control and Prevention's National Program of Cancer Registries and the National Cancer Institute's Surveillance, Epidemiology and End Results program, is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US). As of this report, the CBTRUS database represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors and supersedes all previous reports in terms of completeness and accuracy. All rates are age-adjusted using the 2000 US standard population and presented per 100,000 population. Between 2018 and 2022, the average annual age-adjusted incidence rate (AAAIR) of all primary malignant and non-malignant brain and other CNS tumors was 26.05 per 100,000 population (malignant AAAIR=6.86 and non-malignant AAAIR=19.19). Incidence was higher in women compared to men (29.67 versus 22.23 per 100,000) and in non-Hispanic Black individuals compared to non-Hispanic White (27.40 versus 26.36 per 100,000), non-Hispanic American Indian/Alaska Native (24.38 per 100,000), non-Hispanic Asian or Pacific Islander (20.42 per 100,000), and Hispanic individuals of all races (24.69 per 100,000). Gliomas accounted for 22.2% of all tumors. The most commonly occurring malignant brain and other CNS histopathology was glioblastoma (13.7% of all tumors and 52.2% of all malignant tumors), and the most common non-malignant histopathology was meningioma (42.6% of all tumors [includes malignant meningioma] and 57.4% of all non-malignant tumors). Glioblastoma was more common in men, and meningioma was more common in women. In children and adolescents (ages 0-19 years), the incidence rate of all primary brain and other CNS tumors was 5.99 per 100,000 population. Overall, there were 88,186 total deaths attributed to \u2028malignant brain and other CNS tumors between 2018 and 2022, representing an average of 17,637 deaths per year and an average annual mortality rate of 4.41 per 100,000 population. The five-year relative survival rate following diagnosis of a malignant brain or other CNS tumor was 34.8%, while it was 91.7% for a non-malignant brain or other CNS tumor.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":"27 Supplement_4","pages":"iv1-iv66"},"PeriodicalIF":13.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12527013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302298","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":"High-resolution proteomic analysis of medulloblastoma clinical samples identifies therapy-resistant subgroups and MYC immunohistochemistry as a powerful outcome predictor.","authors":"Alberto Delaidelli, Fares Burwag, Susana Ben-Neriah, Yujin Suk, Taras Shyp, Suzanne Kosteniuk, Christopher Dunham, Sylvia Cheng, Konstantin Okonechnikov, Daniel Schrimpf, Andreas von Deimling, Benjamin Ellezam, Sébastien Perreault, Sheila Singh, Cynthia Hawkins, Marcel Kool, Stefan M Pfister, Christian Steidl, Christopher Hughes, Andrey Korshunov, Poul H Sorensen","doi":"10.1093/neuonc/noaf046","DOIUrl":"10.1093/neuonc/noaf046","url":null,"abstract":"<p><strong>Background: </strong>While international consensus and the 2021 WHO classification recognize multiple molecular medulloblastoma subgroups, these are difficult to identify in clinical practice utilizing routine approaches. As a result, biology-driven risk stratification and therapy assignment for medulloblastoma remains a major clinical challenge. Here, we report mass spectrometry-based analysis of clinical samples for medulloblastoma subgroup discovery, highlighting a MYC-driven prognostic signature and MYC immunohistochemistry (IHC) as a clinically tractable method for improved risk stratification.</p><p><strong>Methods: </strong>We analyzed 56 formalin fixed paraffin embedded (FFPE) medulloblastoma samples by data-independent acquisition mass spectrometry identifying a MYC proteome signature in therapy-resistant group 3 medulloblastoma. We validated MYC IHC prognostic and predictive value across 2 groups of 3/4 medulloblastoma clinical cohorts (n = 362) treated with standard therapies.</p><p><strong>Results: </strong>After the exclusion of WNT tumors, MYC IHC was an independent predictor of therapy resistance and death [HRs 23.6 and 3.23; 95% confidence interval (CI) 1.04-536.18 and 1.84-5.66; P = .047 and <.001]. Notably, only ~50% of the MYC IHC-positive tumors harbored MYC amplification. Accordingly, cross-validated survival models incorporating MYC IHC outperformed current risk stratification schemes including MYC amplification, and reclassified ~20% of patients into a more appropriate very high-risk category.</p><p><strong>Conclusions: </strong>This study provides a high-resolution proteomic dataset that can be used as a reference for future biomarker discovery. Biology-driven clinical trials should consider MYC IHC status in their design. Integration of MYC IHC in classification algorithms for non-WNT tumors could be rapidly adopted on a global scale, independently of advanced but technically challenging molecular profiling techniques.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2431-2444"},"PeriodicalIF":13.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12526081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557460","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":"CBTRUS Statistical Facts.","authors":"","doi":"10.1093/neuonc/noaf233","DOIUrl":"10.1093/neuonc/noaf233","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":"27 Supplement_4","pages":"NA"},"PeriodicalIF":13.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12530090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308704","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":"Postoperative radiotherapy in subtotally resected recurrent WHO grade 1 meningiomas with intermediate-/high-risk molecular profiles.","authors":"Maximilian Y Deng, Sybren L N Maas, Günes Anil, Philipp Sievers, Jonathan Lischalk, Eric Zhao, Sophie Rauh, Inga Jessen, Tanja Eichkorn, Sebastian Regnery, Lukas Bauer, Thomas Held, Philipp Hoegen-Sassmannshausen, Katharina Seidensaal, Juliane Hörner-Rieber, Stefan M Pfister, Antje Wick, Wolfgang Wick, Andreas von Deimling, Klaus Herfarth, Christine Jungk, Sandro M Krieg, Jürgen Debus, Felix Sahm, Laila König","doi":"10.1093/neuonc/noaf125","DOIUrl":"10.1093/neuonc/noaf125","url":null,"abstract":"<p><strong>Background: </strong>Meningiomas represent the most common primary intracranial tumors in adults, with World Health Organization (WHO) grade 1 typically associated with favorable outcomes following gross total resection (GTR).</p><p><strong>Methods: </strong>This retrospective study included patients with CNS WHO grade 1 meningioma and available DNA methylation profiles (n = 210). Clinical tumor characteristics and treatment course (eg, surgical resection, extent of resection, radiotherapy [RT]) were evaluated. Integrated Scores (InS) were calculated based on methylation family using the DKFZ brain tumor classifier, CNS WHO grading, and chromosomal losses, categorized as low, intermediate, or high. Survival analyses employed Kaplan-Meier and Cox regression methods, with local PFS defined as the primary endpoint.</p><p><strong>Results: </strong>In newly diagnosed cases, GTR was associated with a 93.0% 3-year progression-free survival (PFS), compared to 69.3% following subtotal resection (STR). Stratification by IntS showed that patients in the IntS-low group had superior outcomes: 3-year PFS of 93.4 after GTR and 77.4% after STR. In contrast, patients with IntS-intermediate/high profiles showed significantly worse outcomes, with PFS of 85.9% after GTR and 40.0% after STR. Following tumor recurrence, particularly those with IntS-intermediate/high, postoperative RT after STR may improve 3-year PFS to 88.9%, compared to much lower PFS rates in newly diagnosed cases managed without adjuvant RT after STR (3-year PFS: 40.0%).</p><p><strong>Conclusions: </strong>Our findings highlight the combined impact of both the extent of resection and molecular risk profile on prognosis in newly diagnosed cases. While conservative management is feasible in lower-risk primary cases, recurrent or higher-risk patients may benefit from early postoperative RT.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2370-2381"},"PeriodicalIF":13.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12526101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144160504","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":"Molecular signatures define BAP1-altered meningioma as a distinct CNS tumor with deregulation of Polycomb repressive complex target genes.","authors":"Philipp Sievers, Sonali Arora, Thomas Hielscher, Dilan Savran, Daniel Schrimpf, Rouzbeh Banan, David Vonhören, Stefan Pusch, Martin Sill, Romain Appay, Hans-Georg Wirsching, Tibor Hortobagyi, Hildegard Dohmen, Till Acker, Patricia Kohlhof-Meinecke, Leonille Schweizer, Annika K Wefers, Patrick N Harter, Christian Hartmann, Rudi Beschorner, Jens Schittenhelm, Felix Behling, Ghazaleh Tabatabai, Christian Mawrin, Matija Snuderl, Sybren L N Maas, Pieter Wesseling, Sebastian Brandner, Andrey Korshunov, Miriam Ratliff, Sandro M Krieg, Wolfgang Wick, David T W Jones, Stefan M Pfister, Eric C Holland, Andreas von Deimling, Frank Szulzewsky, Felix Sahm","doi":"10.1093/neuonc/noaf105","DOIUrl":"10.1093/neuonc/noaf105","url":null,"abstract":"<p><strong>Background: </strong>Meningiomas are the most common primary intracranial neoplasms, with highly variable patient outcomes. While most meningiomas are benign, a significant subset recurs postoperatively, presenting substantial treatment challenges. BAP1 gene inactivation has been suggested as a marker for aggressive meningiomas, although its precise molecular and clinical roles remain poorly understood.</p><p><strong>Methods: </strong>To comprehensively investigate BAP1-altered meningiomas, we used six meningiomas with known BAP1 alterations as a discovery set. Genome-wide DNA methylation profiling of these samples, along 11 151 reference meningiomas, identified a distinct molecular cluster (n = 42) using unsupervised visualization approaches. These tumors were further characterized by DNA/RNA sequencing, histopathological examination, and a retrospective review of clinical data, compared to reference meningioma cohorts, providing a thorough characterization of this rare tumor subtype.</p><p><strong>Results: </strong>Our integrative analysis revealed BAP1-altered meningiomas as a distinct CNS tumor subtype, characterized by recurrent loss of chromosome 3p21 and driven by various BAP1-inactivating alterations. Although rhabdoid morphology is present in some cases, it is not exclusive and should not be used as a grading criterion. Progression-free survival analysis showed a median of 21 months (95% CI: 12-NA), with a 2-year overall survival rate of 79% (95% CI: 60%-100%), highlighting the aggressive nature of these tumors. Gene expression profiling revealed upregulation of PRC target genes, dysregulated Polycomb signaling, and elevated expression in several cellular and growth factor pathways.</p><p><strong>Conclusions: </strong>BAP1-altered meningiomas represent a distinct and aggressive CNS tumor subtype associated with PRC dysregulation and recurrent 3p chromosome loss. These findings support the designation \"meningioma, BAP1-altered.\"</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2326-2340"},"PeriodicalIF":13.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12526046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995842","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":"Charting the single-cell and spatial landscape of IDH-wild-type glioblastoma with GBmap.","authors":"Cristian Ruiz-Moreno, Sergio Marco Salas, Erik Samuelsson, Mariia Minaeva, Ignacio Ibarra, Marco Grillo, Sebastian Brandner, Ananya Roy, Karin Forsberg-Nilsson, Mariette E G Kranendonk, Fabian J Theis, Mats Nilsson, Hendrik G Stunnenberg","doi":"10.1093/neuonc/noaf113","DOIUrl":"10.1093/neuonc/noaf113","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GB), particularly IDH-wild type, is the most aggressive brain malignancy with a dismal prognosis. Despite advances in molecular profiling, the complexity of its tumor microenvironment and spatial organization remains poorly understood. This study aimed to create a comprehensive single-cell and spatial atlas of GB to unravel its cellular heterogeneity, spatial architecture, and clinical relevance.</p><p><strong>Methods: </strong>We integrated single-cell RNA sequencing data from 26 datasets, encompassing over 1.1 million cells from 240 patients, to construct GBmap, a harmonized single-cell atlas. High-resolution spatial transcriptomics was employed to map the spatial organization of GB tissues. We developed the Tumor Structure Score (TSS) to quantify tumor organization and correlated it with patient outcomes.</p><p><strong>Results: </strong>We showcase the applications of GBmap for reference mapping, transfer learning, and biological discoveries. GBmap revealed extensive cellular heterogeneity, identifying rare populations such as tumor-associated neutrophils and homeostatic microglia. Spatial analysis uncovered 7 distinct tumor niches, with hypoxia-dependent niches strongly associated with poor prognosis. The TSS demonstrated that highly organized tumors, characterized by well-defined vasculature and hypoxic niches, correlated with worse survival outcomes.</p><p><strong>Conclusions: </strong>This study provides a comprehensive resource for understanding glioblastoma heterogeneity and spatial organization. GBmap and the TSS provide an integrative view of tumor architecture in GB, highlighting hypoxia-driven niches that may represent avenues for further investigation. Our resource can facilitate exploratory analyses and hypothesis generation to better understand disease progression.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2281-2295"},"PeriodicalIF":13.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12526130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003231","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}