Neuro-oncology最新文献

{"title":"G-quadruplex stabilizer CX-5461 effectively combines with radiotherapy to target α-thalassemia/mental retardation X-linked-deficient malignant glioma.","authors":"Sharvari Dharmaiah, Prit Benny Malgulwar, William E Johnson, Brandon A Chen, Vladislav Sharin, Benjamin T Whitfield, Christian Alvarez, Vasudev Tadimeti, Ahsan S Farooqi, Jason T Huse","doi":"10.1093/neuonc/noae248","DOIUrl":"10.1093/neuonc/noae248","url":null,"abstract":"<p><strong>Background: </strong>Inactivation of α-thalassemia/mental retardation X-linked (ATRX) represents a defining molecular feature in large subsets of malignant glioma. ATRX deficiency gives rise to abnormal G-quadruplex (G4) DNA secondary structures, enhancing replication stress and genomic instability. Building on earlier work, we evaluated the extent to which pharmacological G4 stabilization selectively enhances DNA damage and cell death in ATRX-deficient preclinical glioma models.</p><p><strong>Methods: </strong>Using the G4 stabilizer CX-5461, we treated patient-derived glioma stem cells (GSCs) in vitro and GSC flank and intracranial murine xenografts in vivo to evaluate efficacy as both a single agent and in combination with ionizing radiation (IR), the latter a central element of current treatment standards.</p><p><strong>Results: </strong>CX-5461 promoted dose-sensitive lethality in ATRX-deficient GSCs relative to ATRX-intact controls. Mechanistic studies revealed that CX-5461 disrupted histone variant H3.3 deposition, enhanced replication stress and DNA damage, activated p53-independent apoptosis, and induced G2/M arrest to a greater extent in ATRX-deficient GSCs than in ATRX-intact counterparts. These data were corroborated in vivo, where CX-5461/IR treatment profoundly delayed tumor growth and prolonged survival in mice bearing ATRX-deficient flank xenografts. Histopathological analyses revealed decreased proliferation, increased apoptosis, and significant G4 induction, replication stress, and DNA damage in CX-5461-treated tumors, both alone and in combination with IR. Finally, despite suboptimal blood-brain-barrier penetration, systemic CX-5461 treatment induced tangible pharmacodynamic effects in ATRX-deficient intracranial GSC models.</p><p><strong>Conclusions: </strong>In totality, our work substantively demonstrates efficacy and defines mechanisms of action for G4 stabilization as a novel therapeutic strategy targeting ATRX-deficient malignant glioma, laying the groundwork for clinical translation.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"932-947"},"PeriodicalIF":16.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681613","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":"Phase 2 trial of veliparib, local irradiation, and temozolomide in patients with newly diagnosed high-grade glioma: a Children's Oncology Group study.","authors":"Matthias A Karajannis, Arzu Onar-Thomas, Tong Lin, Patricia A Baxter, Daniel R Boué, Bonnie L Cole, Christine Fuller, Sofia Haque, Nada Jabado, John T Lucas, Shannon M MacDonald, Celeste Matsushima, Namrata Patel, Christopher R Pierson, Mark M Souweidane, Diana L Thomas, Michael F Walsh, Wafik Zaky, Sarah E S Leary, Amar Gajjar, Maryam Fouladi, Kenneth J Cohen","doi":"10.1093/neuonc/noae247","DOIUrl":"10.1093/neuonc/noae247","url":null,"abstract":"<p><strong>Background: </strong>The outcome for pediatric patients with high-grade glioma (HGG) remains poor. Veliparib, a potent oral poly(adenosine diphosphate-ribose) polymerase (PARP) 1/2 inhibitor, enhances the activity of radiotherapy and DNA-damaging chemotherapy.</p><p><strong>Methods: </strong>We conducted a single-arm, non-randomized phase 2 clinical trial to determine whether treatment with veliparib and radiotherapy, followed by veliparib and temozolomide, improves progression-free survival in pediatric patients with newly diagnosed HGG without H3 K27M or BRAF mutations, compared to patient-level data from historical cohorts with closely matching clinical and molecular features. Following surgical resection, newly diagnosed children with non-metastatic HGG were screened by rapid central pathology review and molecular testing. Eligible patients were enrolled on Stratum 1 (IDH wild-type) or Stratum 2 (IDH mutant).</p><p><strong>Results: </strong>Both strata were closed to accrual for futility after planned interim analyses. Among the 23 eligible patients who enrolled on Stratum 1 and received protocol therapy, the 1-year event-free survival (EFS) was 23% (standard error, SE = 9%) and the 1-year overall survival (OS) was 64% (SE = 10%). Among the 14 eligible patients who enrolled on Stratum 2 and received protocol therapy, the 1-year EFS was 57% (SE = 13%) and 1-year OS was 93% (SE = 0.7%).</p><p><strong>Conclusions: </strong>Rapid central pathology review and molecular testing for eligibility were feasible. The protocol therapy including radiation, veliparib, and temozolomide was well tolerated but failed to improve outcomes compared to clinically and molecularly matched historical control cohorts treated with higher doses of alkylator chemotherapy.</p><p><strong>Clinicaltrials.gov identifier: </strong>NCT03581292 (first posted: July 10, 2018).</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1092-1101"},"PeriodicalIF":16.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668032","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 novel nuclear RNA HSD52 scaffolding NONO/SFPQ complex modulates DNA damage repair to facilitate temozolomide resistance.","authors":"Nan Sun, Qun Chen, Hao Chen, Penggang Sun, Yuxiang Liu, Dan Song, Daohan Yu, Pandeng Wang, Yu Song, Jie Qin, Kaifu Tian, Junzhe Zhong, Wenbin Ma, Hanwen Xuan, Da Qian, Ye Yuan, Tongzheng Chen, Xin Wang, Chuanlu Jiang, Jinquan Cai, Xiangqi Meng","doi":"10.1093/neuonc/noae272","DOIUrl":"10.1093/neuonc/noae272","url":null,"abstract":"<p><strong>Background: </strong>Temozolomide (TMZ) is used in the treatment of glioblastoma (GBM). However, the primary obstacle remains the emergence of TMZ chemotherapy resistance. Non-POU domain-containing octamer-binding protein (NONO) and splicing factor proline/glutamine rich (SFPQ) are multifunctional nuclear proteins involved in genome stability and gene regulation. However, the specific role of NONO and SFPQ in TMZ resistance of GBM remains to be explored.</p><p><strong>Methods: </strong>RNA-binding protein immunoprecipitation-microarray and RNA microarray of TMZ-resistant and parental cells were performed for the gain of HSD52. The effects of HSD52 on TMZ resistance were investigated through in vitro assays, intracranial xenograft, and GBM organoid models. The underlying mechanisms were explored by DNA methylation chip, RNA immunoprecipitation, RNA pull-down assays, among others. GBM clinical samples were rolled in to investigate the clinical significance of HSD52.</p><p><strong>Results: </strong>We identified a novel noncoding RNA, HSD52, that was highly expressed in TMZ-resistant GBM and facilitated the interaction between NONO and SFPQ. H3 ubiquitination attenuation and reduced DNA methyltransferase 1 (DNMT1) recruitment increased HSD52 transcription via DNA hypo-methylation. HSD52 formed an RNA duplex with UFM1 specific ligase 1 (UFL1) mRNA, thereby promoting NONO/SFPQ complex binding to UFL1 mRNA and enhancing its stability, and then contributed to TMZ resistance through activating the ataxia telangiectasia mutated signaling pathway. In vivo xenograft and GBM organoid models showed significant repression in tumor growth after HSD52 knockout with TMZ treatment. In GBM clinical samples, HSD52 was responsible for the malignant progression and TMZ resistance.</p><p><strong>Conclusions: </strong>Our results revealed that HSD52 could serve as a promising therapeutic target to overcome TMZ resistance, improving the clinical efficacy of TMZ chemotherapy in GBM.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"963-978"},"PeriodicalIF":16.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824460","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":"Genome-wide CRISPR-Cas9 screens identify BCL family members as modulators of response to regorafenib in experimental glioma.","authors":"Lara Annina Haeusser, Hannes Becker, Laurence Kuhlburger, Marcello Zago, Bianca Walter, Foteini Tsiami, Sarah Erdmann, Jil Trampert, Surender Surender, Aaron Stahl, Markus Templin, Eileen Wegner, Tobias Schmidt, Christian Schmees, Nicolas Casadei, Lisa Sevenich, Manfred Claassen, Sven Nahnsen, Susanne Beck, Daniel Josef Merk, Ghazaleh Tabatabai","doi":"10.1093/neuonc/noae278","DOIUrl":"10.1093/neuonc/noae278","url":null,"abstract":"<p><strong>Background: </strong>Registered systemic treatment options for glioblastoma patients are limited. The phase II REGOMA trial suggested an improvement of median overall survival in progressive glioblastoma by the multi-tyrosine kinase inhibitor regorafenib. This has not been confirmed by GBM AGILE. So far, regorafenib has been administered as monotherapy or as an addition to standard of care in newly diagnosed glioblastoma. Rational combination therapies involving regorafenib might be a reasonable strategy. Here, we aimed at identifying functionally instructed combination therapies involving regorafenib.</p><p><strong>Methods: </strong>We applied a genome-wide CRISPR-Cas9-based functional genomics target discovery approach using activation and knockout screens followed by genetic, pharmacological, functional validations. Regorafenib-induced molecular alterations were assessed by RNA sequencing and DigiWest. We investigated selected functionally instructed combination therapies in three orthotopic glioma mouse models in vivo (syngeneic SMA560/VM/Dk model and two xenograft models) and performed immunohistochemistry of post-treatment brains.</p><p><strong>Results: </strong>We identified potential modifiers of regorafenib response, including BCL2, BCL2L1, ITGB3, FOXC1, SERAC1, ARAF, and PLCE1. The combination of regorafenib with Bcl-2/Bcl-xL inhibition was superior to both monotherapies alone in vitro, ex vivo, and in vivo. We identified regorafenib-induced regulations of the Bcl-2 downstream target chemokine receptor 1 (CCR1) as one potential underlying molecular mediator. Furthermore, regorafenib led to changes in the myeloid compartment of the glioma-associated microenvironment.</p><p><strong>Conclusions: </strong>This preclinical study uses a functional genomics-based target discovery approach with subsequent validations involving regorafenib. It serves as a biological rationale for clinical translation. Particularly, an investigation of the combination of regorafenib plus navitoclax within a clinical trial is warranted.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"916-931"},"PeriodicalIF":16.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932312","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":"Targeting processive transcription for Myc-driven circuitry in medulloblastoma.","authors":"Lays Martin Sobral, Faye M Walker, Krishna Madhavan, Elizabeth Janko, Sahiti Donthula, Etienne Danis, Pradeep Bompada, Ilango Balakrishnan, Dong Wang, Angela Pierce, Mary M Haag, Billie J Carstens, Natalie J Serkova, Nicholas K Foreman, Sujatha Venkataraman, Bethany Veo, Rajeev Vibhakar, Nathan A Dahl","doi":"10.1093/neuonc/noaf121","DOIUrl":"10.1093/neuonc/noaf121","url":null,"abstract":"<p><strong>Background: </strong>Medulloblastoma is the most common malignant brain tumor of childhood. The highest-risk tumors are driven by recurrent Myc amplifications (Myc-MB) and experience poorer outcomes despite intensive multimodal therapy. The Myc transcription factor defines core regulatory circuitry for these tumors and acts to broadly amplify downstream pro-survival transcriptional programs. Therapeutic targeting of Myc directly has proven elusive, but inhibiting transcriptional cofactors may present an indirect means of drugging the oncogenic transcriptional circuitry sustaining Myc-MB.</p><p><strong>Methods: </strong>Independent CRISPR-Cas9 screens were pooled to identify conserved dependencies in Myc-MB. We performed chromatin conformation capture (Hi-C) from primary patient Myc-MB samples to map enhancer-promoter interactions. We then treated in vitro and xenograft models with CDK9/7 inhibitors to evaluate effect on Myc-driven programs and tumor growth.</p><p><strong>Results: </strong>Eight CRISPR-Cas9 screens performed across three independent labs identify CDK9 as a conserved dependency in Myc-MB. Myc-MB cells are susceptible to CDK9 inhibition, which is synergistic with concurrent inhibition of CDK7. Inhibition of transcriptional CDKs disrupts enhancer-promoter activity in Myc-MB and downregulates Myc-driven transcriptional programs, exerting potent anti-tumor effect.</p><p><strong>Conclusions: </strong>Our findings identify CDK9 inhibition as a translationally promising strategy for the treatment of Myc-MB.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079222","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":"Inhibition of mitochondrial bioenergetics and hypoxia to radiosensitize diffuse intrinsic pontine glioma.","authors":"Han Shen, Faiqa Mudassar, Shiyong Ma, Xingyu Wang, Sandy Nguyen, Neha Bal, Quy-Susan Huynh, Dongwei Wang, Cecilia Chang, Prunella Ing, Winny Varikatt, Joey Lai, Brian Gloss, Jeff Holst, Geraldine M O'Neill, Harriet Gee, Kristina M Cook, Eric Hau","doi":"10.1093/neuonc/noae255","DOIUrl":"10.1093/neuonc/noae255","url":null,"abstract":"<p><strong>Background: </strong>Diffuse intrinsic pontine gliomas (DIPGs) and other H3K27M-mutated diffuse midline gliomas (DMGs) are brain tumors that primarily affect children. Radiotherapy is the standard of care but only provides only temporary symptomatic relief due to radioresistance. Although hypoxia is a major driver of radioresistance in other tumors, there is no definitive evidence that DIPGs are hypoxic. Diffuse intrinsic pontine gliomas often contain histone mutations, which alter tumor metabolism and are also associated with radioresistance. Our objective was to identify the metabolic profiles of DIPG cells, detect hypoxia signatures, and uncover metabolism-linked mechanisms of radioresistance to improve tumor radiosensitivity.</p><p><strong>Methods: </strong>Using DIPG models combined with clinical datasets, we examined mitochondrial metabolism and signatures of hypoxia. We explored DIPG reliance on mitochondrial metabolism using extracellular flux assays and targeted metabolomics. In vitro and in vivo models were used to explore the mechanisms of targeting mitochondrial bioenergetics and hypoxia for radiosensitization. Treatment-induced transcriptomics and metabolomics were also investigated.</p><p><strong>Results: </strong>Comprehensive analyses of DIPG cells show signatures of enhanced oxidative phosphorylation (OXPHOS). We also identified increased expression of specific OXPHOS-related genes and signatures of hypoxia gene expression in datasets obtained from DIPG patients. We found the presence of hypoxia in orthotopic mouse models bearing DIPG tumors. These findings enabled us to develop a proof-of-concept treatment strategy to enhance radiosensitivity of DIPGs in vitro and in animal models.</p><p><strong>Conclusions: </strong>Diffuse intrinsic pontine glioma cells rely on mitochondrial metabolism for growth, and targeting mitochondria disrupts bioenergetics, alleviates hypoxia, and enhances radiosensitivity. These findings warrant further exploration of OXPHOS inhibition as a radiosensitizing strategy for DIPG treatment.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1061-1075"},"PeriodicalIF":16.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687761","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":"Dynamic contrast-enhanced and diffusion-weighted MR imaging for predicting tumor growth of sporadic vestibular schwannomas: A prospective study.","authors":"Sammy M Schouten, Daniel Lewis, Stefan Cornelissen, Ka-Loh Li, Xiaoping Zhu, Marnix C Maas, Sjoert Pegge, Thijs T G Jansen, Jef J S Mulder, Jérôme J Waterval, Alida A Postma, Omar Pathmanaban, David J Coope, Jolanda M M Derks, Patrick P J H Langenhuizen, Andrew T King, Jeroen B Verheul, Henricus P M Kunst","doi":"10.1093/neuonc/noae252","DOIUrl":"10.1093/neuonc/noae252","url":null,"abstract":"<p><strong>Background: </strong>Advanced MR imaging, such as diffusion-weighted (DWI) and dynamic contrast-enhanced (DCE) imaging, may provide valuable noninvasive information on intrinsic tumor biology. This study aims to evaluate apparent diffusion coefficient (ADC) and DCE-MRI-derived microvascular parameter values (Ktrans, ve, and vp) as potential imaging predictors for future sporadic vestibular schwannoma (VS) growth.</p><p><strong>Methods: </strong>In this prospective cohort study, patients with newly diagnosed unilateral sporadic VS and an initial wait-and-scan strategy were enrolled between January 2021 and January 2023. Patients underwent a single timepoint comprehensive MRI protocol, including DWI and DCE-MRI sequences. The estimated values of ADC, Ktrans, ve, and vp were calculated using established pipelines on a voxelwise basis within the delineated tumor region of interest. Associations of the estimated parameter values with volumetric growth were evaluated in uni- and multivariable logistic regression and survival analyses.</p><p><strong>Results: </strong>Of the 110 analyzed patients, 70 (64%) exhibited growth during follow-up. A significant correlation was primarily observed between the DCE-MRI-derived parameters and VS growth. The combination of mean Ktrans (P < .001) and ve (P < .001) tumor values provided an internally validated model with an AUC of 0.85 for growth, yielding a sensitivity of 89% and specificity of 73% at the optimized cutoff value. Only the mean ADC values were found to be significantly higher in shrinking tumors (P = .04).</p><p><strong>Conclusions: </strong>The strongly significant correlation observed between VS growth and Ktrans and ve tumor values indicate the great potential of the noninvasive DCE-MRI for individualized VS management in clinical practice. External validation is needed to further substantiate these findings.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1116-1127"},"PeriodicalIF":16.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695667","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":"Distinct epigenetic and transcriptional profiles of Epstein-Barr virus-positive and negative primary CNS lymphomas.","authors":"Ling Hai, Dennis Friedel, Felix Hinz, Dirk C Hoffmann, Sofia Doubrovinskaia, Hannah Rohdjess, Katharina Weidenauer, Evgeniya Denisova, Georg T Scheffler, Tobias Kessler, Alexandros Kourtesakis, Christel Herold-Mende, Octavian Henegariu, Joachim M Baehring, Jorg Dietrich, Benedikt Brors, Wolfgang Wick, Felix Sahm, Leon D Kaulen","doi":"10.1093/neuonc/noae251","DOIUrl":"10.1093/neuonc/noae251","url":null,"abstract":"<p><strong>Background: </strong>Epstein-Barr virus (EBV)+ and EBV- primary CNS lymphomas (PCNSL) carry distinct mutational landscapes, but their transcriptional and epigenetic profiles have not been integrated and compared. This precludes further insights into pathobiology and molecular differences, relevant for classification and targeted therapy.</p><p><strong>Methods: </strong>Twenty-three EBV- and 15 EBV+ PCNSL, histologically classified as diffuse large B-cell lymphomas, were subjected to RNA-sequencing and EPIC methylation arrays. Unsupervised clustering analyses were performed. Differentially expressed and differentially methylated genes were identified and integrated.</p><p><strong>Results: </strong>Two distinct transcriptional clusters were found, which separated EBV- and EBV+ PCNSL (P < .0001). The EBV+ transcriptional signature contained genes (GPR15, FCER2/CD23, SLAMF1/CD150) closely regulated by EBV oncogenes in B cells. Pathway enrichment analysis uncovered enhanced B-cell receptor (BCR) and WNT/beta-catenin signaling in EBV- lymphomas, whereas Interleukin-10, NOTCH, and viral life cycle pathways were upregulated in EBV+ PCNSL. Correspondingly, BCR-associated SYK kinase activity was enriched in EBV- tumors while JAK2 was overrepresented in EBV+ PCNSL. Epigenetic profiling revealed reduced global promoter methylation in EBV+ PCNSL. Two methylation clusters were recognized, which separated EBV- and EBV+ PCNSL (P < .0001). Epigenetic profiles were distinct from 2,788 other brain tumor and nonmalignant reference samples. Promoter region hypermethylation of CD79B, a BCR subunit critical for sustained proliferation in EBV- disease, highly correlated (R = -0.7) with its transcriptional downregulation in EBV+ PCNSL.</p><p><strong>Conclusions: </strong>EBV+ and EBV- PCNSL harbor distinct transcriptional and epigenetic profiles, corroborating them as distinctive biological subtypes. Uncovered differences provide novel insights into their pathobiology, may guide molecular diagnostics and targeted therapies.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"979-992"},"PeriodicalIF":16.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687742","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":"Genomic features underlying meningioma sex-specificity.","authors":"David R Raleigh","doi":"10.1093/neuonc/noaf002","DOIUrl":"10.1093/neuonc/noaf002","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1029-1030"},"PeriodicalIF":16.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952458","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":"Tracing tumor-neuronal connectivity in glioblastoma.","authors":"Sean E Lawler","doi":"10.1093/neuonc/noaf005","DOIUrl":"10.1093/neuonc/noaf005","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"867-868"},"PeriodicalIF":16.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971769","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}