Acta Neuropathologica Communications最新文献

{"title":"Macular structural integrity estimates are associated with Parkinson's disease genetic risk.","authors":"Santiago Diaz-Torres, Samantha Sze-Yee Lee, Natalia S Ogonowski, David A Mackey, Stuart MacGregor, Puya Gharahkhani, Miguel E Renteria","doi":"10.1186/s40478-024-01841-9","DOIUrl":"10.1186/s40478-024-01841-9","url":null,"abstract":"<p><strong>Background: </strong>Optical coherence tomography (OCT) is a non-invasive technique to measure retinal layer thickness, providing insights into retinal ganglion cell integrity. Studies have shown reduced retinal nerve fibre layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) thickness in Parkinson's disease (PD) patients. However, it is unclear if there is a common genetic overlap between the macula and peripapillary estimates with PD and if the genetic risk of PD is associated with changes in ganglion cell integrity estimates in young adults.</p><p><strong>Method: </strong>Western Australian young adults underwent OCT imaging. Their pRNFL, GCIPL, and overall retinal thicknesses were recorded, as well as their longitudinal changes between ages 20 and 28. Polygenic risk scores (PRS) were estimated for each participant based on genome-wide summary data from the largest PD genome-wide association study conducted to date. We further evaluated whether PD PRS was associated with changes in thickness at a younger age. To evaluate the overlap between retinal integrity estimates and PD, we annotated and prioritised genes using mBAT-combo and performed colocalisation through the GWAS pairwise method and HyPrColoc. We used a multi-omic approach and single-cell expression data of the retina and brain through a Mendelian randomisation framework to evaluate the most likely causal genes. Genes prioritised were analysed for missense variants that could have a pathogenic effect using AlphaMissense.</p><p><strong>Results: </strong>We found a significant association between the Parkinson's disease polygenic risk score (PD PRS) and changes in retinal thickness in the macula of young adults assessed at 20 and 28 years of age. Gene-based analysis identified 27 genes common to PD and retinal integrity, with a notable region on chromosome 17. Expression analyses highlighted NSF, CRHR1, and KANSL1 as potential causal genes shared between PD and ganglion cell integrity measures. CRHR1 showed consistent results across multiple omics levels.</p><p><strong>Interpretation: </strong>Our findings suggest that retinal measurements, particularly in young adults, could be a potential marker for PD risk, indicating a genetic overlap between retinal structural integrity and PD. The study highlights specific genes and loci, mainly on chromosome 17, as potential shared etiological factors for PD and retinal changes. Our results highlight the importance of further longitudinal studies to validate retinal structural metrics as early indicators of PD predisposition.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"130"},"PeriodicalIF":6.2,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic profiles and clinical presentation of chordoma","authors":"Hela Koka, Weiyin Zhou, Mary L. McMaster, Jiwei Bai, Wen Luo, Alyssa Klein, Tongwu Zhang, Xing Hua, Xin Li, Difei Wang, Yujia Xiong, Kristine Jones, Aurelie Vogt, Belynda Hicks, Dilys Parry, Alisa M. Goldstein, Xiaohong R. Yang","doi":"10.1186/s40478-024-01833-9","DOIUrl":"https://doi.org/10.1186/s40478-024-01833-9","url":null,"abstract":"Chordoma is a rare bone cancer with variable clinical outcomes. Here, we recruited 184 sporadic chordoma patients from the US and Canada and collected their clinical and treatment data. The average age at diagnosis was 45.5 years (Range 5–78) and the chordoma site distribution was 49.2% clivus, 26.2% spinal, and 24.0% sacral. Most patients (97.5%) received surgery as the primary treatment, among whom 85.3% also received additional treatment. Except for the most prevalent cancers like prostate, lung, breast, and skin cancer, there was no discernible enrichment for any specific cancer type among patients or their family members. Among a subset of patients (N = 70) with tumor materials, we conducted omics analyses and obtained targeted panel sequencing and SNP array genotyping data for 51 and 49 patients, respectively. The most recurrent somatic driver mutations included PIK3CA (12%), followed by chromatin remodeling genes PBRM1 and SETD2. Amplification of the 6q27 region, containing the chordoma susceptibility gene TBXT, was detected in eight patients (16.3%). Clival patients appeared to be less likely to carry driver gene mutations, chromosome arm level deletion events (e.g., 5p, 5p, and 9p), or 6q27 amplification compared to sacral patients. After adjusting for age, sex, tumor site, and additional treatment, patients with somatic deletions of 14q (OR = 13.73, 95% CI 1.96–96.02, P = 0.008) and 18p (OR = 13.68, 95% CI 1.77–105.89, P = 0.012) were more likely to have persistent chordoma. The study highlights genomic heterogeneity in chordoma, potentially linked to location and clinical progression.","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"30 1","pages":""},"PeriodicalIF":7.1,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141943396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrent adamantinomatous craniopharyngiomas show MAPK pathway activation, clonal evolution and rare TP53-loss-mediated malignant progression.","authors":"John R Apps, Jose Mario Gonzalez-Meljem, Romain Guiho, Jessica C Pickles, Eric Prince, Edward Schwalbe, Nikhil Joshi, Thomas J Stone, Olumide Ogunbiyi, Jane Chalker, Akang Bassey, Georg Otto, Rosalind Davies, Debbie Hughes, Sebastian Brandner, Enrica Tan, Victoria Lee, Caroline Hayhurst, Cassie Kline, Sergi Castellano, Todd Hankinson, Timo Deutschbein, Thomas S Jacques, Juan Pedro Martinez-Barbera","doi":"10.1186/s40478-024-01838-4","DOIUrl":"10.1186/s40478-024-01838-4","url":null,"abstract":"<p><p>The two types of craniopharyngioma, adamantinomatous (ACP) and papillary (PCP), are clinically relevant tumours in children and adults. Although the biology of primary craniopharyngioma is starting to be unravelled, little is known about the biology of recurrence. To fill this gap in knowledge, we have analysed through methylation array, RNA sequencing and pERK1/2 immunohistochemistry a cohort of paired primary and recurrent samples (32 samples from 14 cases of ACP and 4 cases of PCP). We show the presence of copy number alterations and clonal evolution across recurrence in 6 cases of ACP, and analysis of additional whole genome sequencing data from the Children's Brain Tumour Network confirms chromosomal arm copy number changes in at least 7/67 ACP cases. The activation of the MAPK/ERK pathway, a feature previously shown in primary ACP, is observed in all but one recurrent cases of ACP. The only ACP without MAPK activation is an aggressive case of recurrent malignant human craniopharyngioma harbouring a CTNNB1 mutation and loss of TP53. Providing support for a functional role of this TP53 mutation, we show that Trp53 loss in a murine model of ACP results in aggressive tumours and reduced mouse survival. Finally, we characterise the tumour immune infiltrate showing differences in the cellular composition and spatial distribution between ACP and PCP. Together, these analyses have revealed novel insights into recurrent craniopharyngioma and provided preclinical evidence supporting the evaluation of MAPK pathway inhibitors and immunomodulatory approaches in clinical trials in against recurrent ACP.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"127"},"PeriodicalIF":6.2,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting gliomatosis cerebri in adult-type diffuse gliomas: a comprehensive imaging, genomic and clinical analysis.","authors":"Ilah Shin, Yae Won Park, Yongsik Sim, Seo Hee Choi, Sung Soo Ahn, Jong Hee Chang, Se Hoon Kim, Seung-Koo Lee, Rajan Jain","doi":"10.1186/s40478-024-01832-w","DOIUrl":"10.1186/s40478-024-01832-w","url":null,"abstract":"<p><p>Although gliomatosis cerebri (GC) has been removed as an independent tumor type from the WHO classification, its extensive infiltrative pattern may harbor a unique biological behavior. However, the clinical implication of GC in the context of the 2021 WHO classification is yet to be unveiled. This study investigated the incidence, clinicopathologic and imaging correlations, and prognostic implications of GC in adult-type diffuse glioma patients. Retrospective chart and imaging review of 1,211 adult-type diffuse glioma patients from a single institution between 2005 and 2021 was performed. Among 1,211 adult-type diffuse glioma patients, there were 99 (8.2%) patients with GC. The proportion of molecular types significantly differed between patients with and without GC (P = 0.017); IDH-wildtype glioblastoma was more common (77.8% vs. 66.5%), while IDH-mutant astrocytoma (16.2% vs. 16.9%) and oligodendroglioma (6.1% vs. 16.5%) were less common in patients with GC than in those without GC. The presence of contrast enhancement, necrosis, cystic change, hemorrhage, and GC type 2 were independent risk factors for predicting IDH mutation status in GC patients. GC remained as an independent prognostic factor (HR = 1.25, P = 0.031) in IDH-wildtype glioblastoma patients on multivariable analysis, along with clinical, molecular, and surgical factors. Overall, our data suggests that although no longer included as a distinct pathological entity in the WHO classification, recognition of GC may be crucial considering its clinical significance. There is a relatively high incidence of GC in adult-type diffuse gliomas, with different proportion according to molecular types between patients with and without GC. Imaging may preoperatively predict the molecular type in GC patients and may assist clinical decision-making. The prognostic role of GC promotes its recognition in clinical settings.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"128"},"PeriodicalIF":6.2,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 knockout screens identify DNMT1 as a druggable dependency in sonic hedgehog medulloblastoma.","authors":"Foteini Tsiami, Chiara Lago, Noemi Pozza, Federica Piccioni, Xuesong Zhao, Fabienne Lülsberg, David E Root, Luca Tiberi, Marcel Kool, Jens Schittenhelm, Pratiti Bandopadhayay, Rosalind A Segal, Ghazaleh Tabatabai, Daniel J Merk","doi":"10.1186/s40478-024-01831-x","DOIUrl":"10.1186/s40478-024-01831-x","url":null,"abstract":"<p><p>Sonic hedgehog subgroup of medulloblastoma (SHH-MB) is characterized by aberrant activation of the SHH signaling pathway. An inhibition of the positive SHH regulator Smoothened (SMO) has demonstrated promising clinical efficacy. Yet, primary and acquired resistance to SMO inhibitors limit their efficacy. An understanding of underlying molecular mechanisms of resistance to therapy is warranted to bridge this unmet need. Here, we make use of genome-wide CRISPR-Cas9 knockout screens in murine SMB21 and human DAOY cells, in order to unravel genetic dependencies and drug-related genetic interactors that could serve as alternative therapeutic targets for SHH-MB. Our screens reinforce SMB21 cells as a faithful model system for SHH-MB, as opposed to DAOY cells, and identify members of the epigenetic machinery including DNA methyltransferase 1 (DNMT1) as druggable targets in SHH-dependent tumors. We show that Dnmt1 plays a crucial role in normal murine cerebellar development and is required for SHH-MB growth in vivo. Additionally, DNMT1 pharmacological inhibition alone and in combination with SMO inhibition effectively inhibits tumor growth in murine and human SHH-MB cell models and prolongs survival of SHH-MB mouse models by inhibiting SHH signaling output downstream of SMO. In conclusion, our data highlight the potential of inhibiting epigenetic regulators as a novel therapeutic avenue in SMO-inhibitor sensitive as well as resistant SHH-MBs.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"125"},"PeriodicalIF":6.2,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11304869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social deficits mirror delayed cerebrovascular dysfunction after traumatic brain injury.","authors":"Aditya Singh, Steven Gong, Anh Vu, Scott Li, Andre Obenaus","doi":"10.1186/s40478-024-01840-w","DOIUrl":"10.1186/s40478-024-01840-w","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) survivors face debilitating long-term psychosocial consequences, including social isolation and depression. TBI modifies neurovascular physiology and behavior but the chronic physiological implications of altered brain perfusion on social interactions are unknown. Adult C57/BL6 male mice received a moderate cortical TBI, and social behaviors were assessed at baseline, 3-, 7-, 14-, 30-, and 60-days post injury (dpi). Magnetic resonance imaging (MRI, 9.4T) using dynamic susceptibility contrast perfusion weighted MRI were acquired. At 60dpi mice underwent histological angioarchitectural mapping. Analysis utilized standardized protocols followed by cross-correlation metrics. Social behavior deficits at 60dpi emerged as reduced interactions with a familiar cage-mate (partner) that mirrored significant reductions in cerebral blood flow (CBF) at 60dpi. CBF perturbations were dynamic temporally and across brain regions including regions known to regulate social behavior such as hippocampus, hypothalamus, and rhinal cortex. Social isolation in TBI-mice emerged with a significant decline in preference to spend time with a cage mate. Cortical vascular density was also reduced corroborating the decline in brain perfusion and social interactions. Thus, the late emergence of social interaction deficits mirrored the reduced vascular density and CBF in regions known to be involved in social behaviors. Vascular morphology and function improved prior to the late decrements in social function and our correlations strongly implicate a linkage between vascular density, cerebral perfusion, and social interactions. Our study provides a clinically relevant timeline of alterations in social deficits alongside functional vascular recovery that can guide future therapeutics.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"126"},"PeriodicalIF":6.2,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11304659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of BRAF/MEK-inhibitor therapy for epithelioid glioblastoma with a novel BRAFV600 mutation.","authors":"J Steininger, C Buszello, R Oertel, M Meinhardt, S Schmid, K Engellandt, S Herold, S Stasik, A Ebrahimi, B Renner, C Thiede, I Y Eyüpoglu, G Schackert, S Beissert, F Meier, J Radke, D Westphal, T A Juratli","doi":"10.1186/s40478-024-01834-8","DOIUrl":"10.1186/s40478-024-01834-8","url":null,"abstract":"<p><p>Epithelioid glioblastoma (eGB), a very aggressive and rare brain tumour, is associated with a dismal median overall survival. Effective therapies for patients with eGB, particularly with leptomeningeal dissemination, are still lacking. Here, we describe a case of a 25-year-old male diagnosed with an intramedullary cervical tumour with subsequent leptomeningeal disease. Histopathology identified a highly necrotising, epithelioid-type tumour with high cell density, most compatible with the diagnosis of an eGB. DNA analysis revealed an unprecedented B-Raf protooncogene, serine/threonine kinase (BRAF) gene variant in exon 15 (ENST00000288602.6, c.1799_1810delinsATG, p.(V600_W604delinsDG)), triggering activation of the mitogen-activated protein kinase (MAPK) pathway. Consequently, we initiated MAPK inhibitor (MAPKi) therapy, utilizing a combination of BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors. Liquid chromatography-tandem mass spectrometry analysis confirmed the drugs' presence in the patient's cerebrospinal fluid, indicating their capacity to cross the blood-brain barrier. Remarkably, the patient responded very well to therapy and transitioned from a near-comatose state to significantly improved health, sustained for over three months. This study highlights that MAPKi, particularly targeted towards novel BRAFV600 mutations, might offer promising advancements in eGB treatment strategies.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"124"},"PeriodicalIF":6.2,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11302837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic analysis of foramen magnum meningiomas reveals AKT1 mutations uncomplicated by TRAF7 mutations.","authors":"Yudai Hirano, Satoru Miyawaki, Yu Sakai, Yu Teranishi, Atsushi Okano, Motoyuki Umekawa, Hiroki Hongo, Seiei Torazawa, Shotaro Ogawa, Daisuke Komura, Hiroto Katoh, Masako Ikemura, Tetsuo Ushiku, Shumpei Ishikawa, Nobuhito Saito","doi":"10.1186/s40478-024-01835-7","DOIUrl":"10.1186/s40478-024-01835-7","url":null,"abstract":"","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"123"},"PeriodicalIF":6.2,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pure argyrophilic grain disease revisited: independent effects on limbic, neocortical, and striato-pallido-nigral degeneration and the development of dementia in a series with a low to moderate Braak stage.","authors":"Osamu Yokota, Tomoko Miki, Hanae Nakashima-Yasuda, Hideki Ishizu, Takashi Haraguchi, Chikako Ikeda, Masato Hasegawa, Akinori Miyashita, Takeshi Ikeuchi, Naoto Nishikawa, Shintaro Takenoshita, Koichiro Sudo, Seishi Terada, Manabu Takaki","doi":"10.1186/s40478-024-01828-6","DOIUrl":"10.1186/s40478-024-01828-6","url":null,"abstract":"<p><p>Agyrophilic grains (AGs) are age-related limbic-predominant lesions in which four-repeat tau is selectively accumulated. Because previous methodologically heterogeneous studies have demonstrated inconsistent findings on the relationship between AGs and dementia, whether AGs affect cognitive function remains unclear. To address this question, we first comprehensively evaluated the distribution and quantity of Gallyas-positive AGs and the severity of neuronal loss in the limbic, neocortical, and subcortical regions in 30 cases of pure argyrophilic grain disease (pAGD) in Braak stages I-IV and without other degenerative diseases, and 34 control cases that had only neurofibrillary tangles with Braak stages I-IV and no or minimal Aβ deposits. Then, we examined whether AGs have independent effects on neuronal loss and dementia by employing multivariate ordered logistic regression and binomial logistic regression. Of 30 pAGD cases, three were classified in diffuse form pAGD, which had evident neuronal loss not only in the limbic region but also in the neocortex and subcortical nuclei. In all 30 pAGD cases, neuronal loss developed first in the amygdala, followed by temporo-frontal cortex, hippocampal CA1, substantia nigra, and finally, the striatum and globus pallidus with the progression of Saito AG stage. In multivariate analyses of 30 pAGD and 34 control cases, the Saito AG stage affected neuronal loss in the amygdala, hippocampal CA1, temporo-frontal cortex, striatum, globus pallidus, and substantia nigra independent of the age, Braak stage, and limbic-predominant age-related TDP-43 encephalopathy (LATE-NC) stage. In multivariate analyses of 23 pAGD and 28 control cases that lacked two or more lacunae and/or one or more large infarctions, 100 or more AGs per × 400 visual field in the amygdala (OR 10.02, 95% CI 1.12-89.43) and hippocampal CA1 (OR 12.22, 95% CI 1.70-87.81), and the presence of AGs in the inferior temporal cortex (OR 8.18, 95% CI 1.03-65.13) affected dementia independent of age, moderate Braak stages (III-IV), and LATE-NC. Given these findings, the high density of limbic AGs and the increase of AGs in the inferior temporal gyrus may contribute to the occurrence of dementia through neuronal loss, at least in cases in a low to moderate Braak stage.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"121"},"PeriodicalIF":6.2,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11290173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroradiological, genetic and clinical characteristics of histone H3 K27-mutant diffuse midline gliomas in the Kansai Molecular Diagnosis Network for CNS Tumors (Kansai Network): multicenter retrospective cohort.","authors":"Nobuhide Hayashi, Junya Fukai, Hirokazu Nakatogawa, Hiroshi Kawaji, Ema Yoshioka, Yoshinori Kodama, Kosuke Nakajo, Takehiro Uda, Kentaro Naito, Noriyuki Kijima, Yoshiko Okita, Naoki Kagawa, Yoshinobu Takahashi, Naoya Hashimoto, Hideyuki Arita, Koji Takano, Daisuke Sakamoto, Tomoko Iida, Yoshiki Arakawa, Takeshi Kawauchi, Yukihiko Sonoda, Yuta Mitobe, Kenichi Ishibashi, Masahide Matsuda, Takamune Achiha, Takahiro Tomita, Masahiro Nonaka, Keijiro Hara, Noriyoshi Takebe, Takashi Tsuzuki, Yoshikazu Nakajima, Shiro Ohue, Nobuyuki Nakajima, Akira Watanabe, Akihiro Inoue, Masao Umegaki, Daisuke Kanematsu, Asako Katsuma, Miho Sumida, Tomoko Shofuda, Masayuki Mano, Manabu Kinoshita, Kanji Mori, Naoyuki Nakao, Yonehiro Kanemura","doi":"10.1186/s40478-024-01808-w","DOIUrl":"10.1186/s40478-024-01808-w","url":null,"abstract":"<p><p>This study aims to elucidate the clinical and molecular characteristics, treatment outcomes and prognostic factors of patients with histone H3 K27-mutant diffuse midline glioma. We retrospectively analyzed 93 patients with diffuse midline glioma (47 thalamus, 24 brainstem, 12 spinal cord and 10 other midline locations) treated at 24 affiliated hospitals in the Kansai Molecular Diagnosis Network for CNS Tumors. Considering the term \"midline\" areas, which had been confused in previous reports, we classified four midline locations based on previous reports and anatomical findings. Clinical and molecular characteristics of the study cohort included: age 4-78 years, female sex (41%), lower-grade histology (56%), preoperative Karnofsky performance status (KPS) scores ≥ 80 (49%), resection (36%), adjuvant radiation plus chemotherapy (83%), temozolomide therapy (76%), bevacizumab therapy (42%), HIST1H3B p.K27M mutation (2%), TERT promoter mutation (3%), MGMT promoter methylation (9%), BRAF p.V600E mutation (1%), FGFR1 mutation (14%) and EGFR mutation (3%). Median progression-free and overall survival time was 9.9 ± 1.0 (7.9-11.9, 95% CI) and 16.6 ± 1.4 (13.9-19.3, 95% CI) months, respectively. Female sex, preoperative KPS score ≥ 80, adjuvant radiation + temozolomide and radiation ≥ 50 Gy were associated with favorable prognosis. Female sex and preoperative KPS score ≥ 80 were identified as independent good prognostic factors. This study demonstrated the current state of clinical practice for patients with diffuse midline glioma and molecular analyses of diffuse midline glioma in real-world settings. Further investigation in a larger population would contribute to better understanding of the pathology of diffuse midline glioma.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"120"},"PeriodicalIF":6.2,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}