المؤلفون: Duan, Zejun, Feng, Jing, Guan, Yuguang, Li, Shouwei, Wu, Bin, Shao, Yang, Ma, Zhong, Hu, Zejuan, Xiang, Lei, Zhu, Mingwang, Fan, Xiaolong, Qi, Xueling

المصدر: Brain Communications ; ISSN 2632-1297

الوصف: Current histological classification of low-grade glioneuronal tumors (LGNT) does not adequately represent their underlying biology. The neural lineage(s) and differentiation stage(s) involved, and the cell state(s) affected by the recurrent genomic alterations are unclear. Here, we describe dysregulated oligodendrocyte lineage developmental programs in three LGNT subtypes. Ten dysembryoplastic neuroepithelial tumors (DNET), four myxoid glioneuronal tumors (MGNT), and five rosette-forming glioneuronal tumors (RGNT) were collected. Besides a comprehensive characterization of clinical features, known diagnostic markers, and genomic alterations, we used comprehensive immunohistochemical stainings to characterize activation of rat sarcoma/mitogen-activated protein kinase (RAS/MAPK) pathway, involvement of neuronal component, resemblance to glial lineages and differentiation blockage along the stages of oligodendrocyte lineage. The findings were further complemented by gene set enrichment analysis with transcriptome data of DNETs from the literature. DNETs, MGNTs, and RGNTs occur at different ages, with symptoms closely related to tumor location. DNETs and MGNTs contain oligodendrocyte-like cells and neuronal component. RGNTs contained regions of rosette-forming neurocytic and astrocytic features. Scatted neurons, identified by neuronal nuclei antigen (NeuN) and microtubule-associated protein-2 (MAP-2) staining, were consistently observed in all DNETs and MGNTs examined, but only in one RGNT. Pervasive neurofilament (NF)-positive axons were observed only in DNET and MGNT samples. Alterations in B-Raf proto-oncogene, serine/threonine kinase (BRAF), fibroblast growth factor receptor 1 (FGFR1), FGFR3, and platelet derived growth factor receptor alpha (PDGFRA) occurred in a mutually exclusive manner, coinciding with strong staining of phospho-p44/42 MAPK (p-Erk1/2) and low apoptotic signal. All DNETs, MGNTs, and the neurocytic regions of RGNTs showed strong expression of neuron-glia antigen 2 (NG2), PDGFRA ...

الإتاحة: https://doi.org/10.1093/braincomms/fcae156Test

المؤلفون: Gao, Jiayu, Zhao, Yahui, Wang, Ziwei, Liu, Fei, Chen, Xuan, Mo, Jialin, Jiang, Yifei, Liu, Yongqiang, Tian, Peiyi, Li, Yanong, Deng, Kaiwen, Qi, Xueling, Han, Dongming, Liu, Zijia, Yang, Zhengtao, Chen, Yixi, Tang, Yujie, Li, Chunde, Liu, Hailong, Li, Jiankang, Jiang, Tao

المساهمون: National Key Research and Development Program of China, National Natural Science Foundation of China

المصدر: Animal Models and Experimental Medicine ; ISSN 2576-2095 2576-2095

الوصف: Background Medulloblastoma (MB) is one of the most common malignant brain tumors that mainly affect children. Various approaches have been used to model MB to facilitate investigating tumorigenesis. This study aims to compare the recapitulation of MB between subcutaneous patient‐derived xenograft (sPDX), intracranial patient‐derived xenograft (iPDX), and genetically engineered mouse models (GEMM) at the single‐cell level. Methods We obtained primary human sonic hedgehog (SHH) and group 3 (G3) MB samples from six patients. For each patient specimen, we developed two sPDX and iPDX models, respectively. Three Patch+/− GEMM models were also included for sequencing. Single‐cell RNA sequencing was performed to compare gene expression profiles, cellular composition, and functional pathway enrichment. Bulk RNA‐seq deconvolution was performed to compare cellular composition across models and human samples. Results Our results showed that the sPDX tumor model demonstrated the highest correlation to the overall transcriptomic profiles of primary human tumors at the single‐cell level within the SHH and G3 subgroups, followed by the GEMM model and iPDX. The GEMM tumor model was able to recapitulate all subpopulations of tumor microenvironment (TME) cells that can be clustered in human SHH tumors, including a higher proportion of tumor‐associated astrocytes and immune cells, and an additional cluster of vascular endothelia when compared to human SHH tumors. Conclusions This study was the first to compare experimental models for MB at the single‐cell level, providing value insights into model selection for different research purposes. sPDX and iPDX are suitable for drug testing and personalized therapy screenings, whereas GEMM models are valuable for investigating the interaction between tumor and TME cells.

الإتاحة: https://doi.org/10.1002/ame2.12399Test

المؤلفون: Wei, Yanfei, Li, Guanzhang, Feng, Jing, Wu, Fan, Zhao, Zheng, Bao, Zhaoshi, Zhang, Wei, Su, Xiaodong, Li, Jiuyi, Qi, Xueling, Duan, Zejun, Zhang, Yunqiu, Vega, Sandra Ferreyra, Jakola, Asgeir Store, Sun, Yingyu, Carén, Helena, Jiang, Tao, Fan, Xiaolong

المساهمون: National Natural Science Foundation of China, Key Technologies Research and Development Program, VINNOVA

المصدر: Genome Medicine ; volume 15, issue 1 ; ISSN 1756-994X

مصطلحات موضوعية: Genetics (clinical), Genetics, Molecular Biology, Molecular Medicine

الوصف: Background Roughly 50% of adult gliomas harbor isocitrate dehydrogenase ( IDH ) mutations. According to the 2021 WHO classification guideline, these gliomas are diagnosed as astrocytomas, harboring no 1p19q co-deletion, or oligodendrogliomas, harboring 1p19q co-deletion. Recent studies report that IDH-mutant gliomas share a common developmental hierarchy. However, the neural lineages and differentiation stages in IDH-mutant gliomas remain inadequately characterized. Methods Using bulk transcriptomes and single-cell transcriptomes, we identified genes enriched in IDH-mutant gliomas with or without 1p19q co-deletion, we also assessed the expression pattern of stage-specific signatures and key regulators of oligodendrocyte lineage differentiation. We compared the expression of oligodendrocyte lineage stage-specific markers between quiescent and proliferating malignant single cells. The gene expression profiles were validated using RNAscope analysis and myelin staining and were further substantiated using data of DNA methylation and single-cell ATAC-seq. As a control, we assessed the expression pattern of astrocyte lineage markers. Results Genes concordantly enriched in both subtypes of IDH-mutant gliomas are upregulated in oligodendrocyte progenitor cells (OPC). Signatures of early stages of oligodendrocyte lineage and key regulators of OPC specification and maintenance are enriched in all IDH-mutant gliomas. In contrast, signature of myelin-forming oligodendrocytes, myelination regulators, and myelin components are significantly down-regulated or absent in IDH-mutant gliomas. Further, single-cell transcriptomes of IDH-mutant gliomas are similar to OPC and differentiation-committed oligodendrocyte progenitors, but not to myelinating oligodendrocyte. Most IDH-mutant glioma cells are quiescent; quiescent cells and proliferating cells resemble the same differentiation stage of oligodendrocyte lineage. Mirroring the gene expression profiles along the oligodendrocyte lineage, analyses of DNA methylation and ...

الإتاحة: https://doi.org/10.1186/s13073-023-01175-6Test

المؤلفون: Zhao, Chuan, Wang, Ye, Liu, Hongxing, Qi, Xueling, Zhou, Zhongqing, Wang, Xianlong, Lin, Zhixiong

المساهمون: Sanbo Brain Hospital Management Group, Capital Health Research and Development Special Fund

المصدر: Scientific Reports ; volume 13, issue 1 ; ISSN 2045-2322

مصطلحات موضوعية: Multidisciplinary

الوصف: The molecular biological differences between cyst walls and those in solid bodies are the foundation of the outcomes. In this study, the CTNNB1 mutations were confirmed by DNAsequencing; CTNNB1 expression levels were detected by PCR; the differences between solid bodies and cyst walls in proliferative capacity and tumor stem cell niches were assessed by immunohistochemistry; the effect of the residual cyst wall on recurrence was assessed by follow-up. Mutations in the CTNNB1 in the cyst wall and the solid body were identical in each case. No differences were found in the transcriptional level of CTNNB1 between the cyst walls and the solid bodies ( P = 0.7619). The cyst wall showed a pathological structure similar to the solid body. Proliferative capacity of cyst walls was stronger than that of solid body ( P = 0.0021), and β-catenin nuclear positive cells (cell clusters) in cyst walls were more than that in solid tumor ( P = 0.0002). The retrospective 45 ACPs showed residual cyst wall was significantly associated with tumor recurrence or regrowth ( P = 0.0176). Kaplan–Meier analysis showed there was a significant difference in the prognosis between GTR and STR ( P < 0.0001).The cyst wall of ACP contained more tumor stem cell niches which could lead to the recurrence. According to the above-mentioned, a special attention to the management of the cyst wall should be paid.

الإتاحة: https://doi.org/10.1038/s41598-023-29664-zTest
https://www.nature.com/articles/s41598-023-29664-z.pdfTest
https://www.nature.com/articles/s41598-023-29664-zTest

المؤلفون: Han, Song, Yang, Zuocheng, Wang, Liguo, Yang, Yakun, Qi, Xueling, Yan, Changxiang, Yu, Chunjiang

المصدر: British Journal of Neurosurgery; Jun2024, Vol. 38 Issue 3, p625-631, 7p

مصطلحات موضوعية: HYDROCEPHALUS, CEREBROSPINAL fluid shunts, GLIOMAS, MORTALITY risk factors, PROGNOSIS, OVERALL survival

مستخلص: To explore the prognostic factors of patients with low-grade optic pathway glioma (OPG) and the optimal treatment to reduce the incidence of postoperative hydrocephalus. This single-center study retrospectively analyzed data from 66 patients with OPGs who underwent surgery. The patients were followed, and overall survival (OS) and progression-free survival (PFS) were determined. The effects of different treatments on the hydrocephalus of patients were compared. Postoperative hydrocephalus was identified as a factor to increase the risk of mortality by 1.99-fold (p =.028). And, 5-year survival rate was significantly lower among patients with postoperative hydrocephalus (p =.027). The main factors leading to preoperative hydrocephalus in patients are large tumor volume and invasion into the third ventricle. Gross total resections (GTR) could reduce the risk of long-term hydrocephalus (p =.046). Age younger than 4 years (p =.046) and tumor invasion range/classification (p =.029) are the main factors to reduce the five-year survival rate. Postoperative radiotherapy (RT) and chemotherapy (CT) had no significant effects on OS. Extraventricular drainage (EVD) was not associated with perioperative infection (p =.798 >.05) and bleeding (p =.09 >.05). Compared with 2 stage surgery (external ventricular drainage or ventriculoperitoneal shunt (VPS) was first placed, followed by tumor resection), 1 stage surgery (direct resection of tumor) had no complication increase. Postoperative hydrocephalus is mostly obstructive hydrocephalus, and it is an important factor that reduces the OS of patients with low-grade OPGs. Surgery to remove the tumor to the greatest extent improves cerebrospinal fluid circulation is effective at reducing the incidence postoperative hydrocephalus. For patients whose ventricles are still dilated after surgery, in addition to considering poor ventricular compliance, they need to be aware of the persistence and progression of hydrocephalus. [ABSTRACT FROM AUTHOR]

: Copyright of British Journal of Neurosurgery is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Duan, Zejun, Xu, Ke, Xie, Mingguo, Tian, Xiaolin, Wang, Xiongfei, Feng, Jing, Guan, Yuguang, Zhou, Jian, Luan, Guoming, Qi, Xueling, Lu, Dehong

المصدر: American Journal of Clinical Pathology; May2024, Vol. 161 Issue 5, p469-482, 14p

مصطلحات موضوعية: STURGE-Weber syndrome, FOCAL cortical dysplasia, PEOPLE with epilepsy, DYSPLASIA, HIPPOCAMPAL sclerosis, ARTERIAL calcification, PILOCARPINE

مستخلص: Objectives We aimed to investigate the clinicopathologic features of and genetic changes in Sturge-Weber syndrome (SWS) in patients with refractory epilepsy. Methods Clinical data were retrospectively analyzed. H&E and immunohistochemistry were performed to assess pathologic changes. Targeted amplicon sequencing was applied to investigate the somatic GNAQ (c.548G>A) mutation. The potential predictors of seizure outcomes were estimated by univariate and multivariate statistical analyses. Results Forty-eight patients with SWS and refractory epilepsy were enrolled. According to the imaging data and pathologic examination, ipsilateral hippocampal sclerosis (HS), calcification of leptomeningeal arteries, and focal cortical dysplasia were found in 14 (29.2%), 31 (64.6%), and 37 (77.1%) patients, respectively. A high frequency of GNAQ alteration was detected in both cerebral cortex (57.7%) and ipsilateral hippocampus (50.0%) from patients with SWS. During follow-up, 43 of 48 patients (85.4%) had achieved seizure control (Engel class I). Statistically, HS signs on imaging were found to be independent predictors of unfavorable seizure outcomes (P =.015). Conclusions Calcification of leptomeningeal arteries, focal cortical dysplasia, and GNAQ alteration are common features in SWS pathology. Patients with refractory epilepsy caused by SWS can achieve satisfactory seizure control after surgery, but seizure control was compromised in patients with comorbid HS. [ABSTRACT FROM AUTHOR]

: Copyright of American Journal of Clinical Pathology is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Xie, Mingguo, Wang, Xiongfei, Qiao, Jiao, Zhou, Jian, Guan, Yuguang, Li, Tianfu, Qi, Xueling, Luan, Guoming

المساهمون: Open Cooperation Program of Chinese Institute of Brain Research, Beijing, major project of National Natural Science Foundation of China

المصدر: Scientific Reports ; volume 12, issue 1 ; ISSN 2045-2322

مصطلحات موضوعية: Multidisciplinary

الوصف: The aim of the study was to evaluate the clinicopathological features, as well as the surgical prognosis, of epilepsy-associated glioneuronal tumors (GNT) with CD34 expression and BRAF mutation. Clinical data of patients who underwent epilepsy surgery for GNT were retrospectively studied. Univariate and multivariate analyses were performed to evaluate the correlations of clinical and pathological factors with molecular markers of CD34 expression and BRAF V600E mutation in GNT. A total of 247 patients with GNT had immunohistochemical detection of CD34 expression (CD34 positive vs. negative: 198/49), and among them, 102 patients had immunohistochemical detection of BRAF V600E mutation (BRAF positive vs. negative: 59/43). Univariate analysis found that tumor types (P < 0.001), patient population (P = 0.015), seizure aura (P = 0.007), drug-resistant epilepsy (P = 0.036), concordance of ictal electroencephalogram (EEG) findings (P = 0.032), surgical resection extent (P = 0.045), tumor location (P = 0.007) and duration of epilepsy (P = 0.027) were related to CD34 expression, and that concordance of ictal EEG findings (P = 0.031) and age at surgery (P = 0.015) were related to BRAF V600E mutation. In addition, history of generalized tonic–clonic seizure (HR 0.12; P = 0.035), drug-resistant epilepsy (HR 0.13; P = 0.030) and concordance of interictal EEG findings (HR 8.01; P = 0.039) were associated with tumor progression-free survival (PFS). However, CD34 expression or BRAF V600E mutation in GNT was not associated with surgical outcomes of seizure control and tumor PFS. The CD34 expression or BRAF V600E mutation in GNT may partly influence the distribution of clinicopathological features of patients with epilepsy, but they may be not able to predict the surgical prognosis of seizure outcome and tumor recurrence.

الإتاحة: https://doi.org/10.1038/s41598-022-22443-2Test
https://www.nature.com/articles/s41598-022-22443-2.pdfTest
https://www.nature.com/articles/s41598-022-22443-2Test

المؤلفون: Yao, Kun, Duan, Zejun, Feng, Jing, Yan, Changxiang, Qi, Xueling

المصدر: Diagnostic Pathology ; volume 17, issue 1 ; ISSN 1746-1596

مصطلحات موضوعية: General Medicine, Histology, Pathology and Forensic Medicine

الوصف: Background DICER1 -associated central nervous system sarcoma (DCS) without evidence of other cancer-related syndromes is rare. Though the morphology of DCS was highly variable, the immunophenotype was predominant myogenic phenotype. Other lineage markers were consistently negative. Case presentation We report a case of DCS with neurogenic differentiation proved by immunohistochemical staining and whole-exome sequencing (WES). An 8-year-old female patient presented with 8-day history of headache, nausea and vomiting. Magnetic resonance imaging (MRI) revealed a heterogeneous mass in the left parietal lobe. The patient underwent the craniotomy via left parietal approach to resect the tumor completely. Histologically, the tumor predominately showed fibrosarcoma-like spindle cells with obvious cytoplasmic eosinophilic globules. Immunohistochemically, the tumor stained positively for DICER1, Desmin, and several neurogenic markers. DICER1 somatic hotspot mutation was confirmed by WES, as well as TP53 and RAF1 mutations which were commonly found in DCS, and other sarcoma-associated genes including AR , AXL and ETV5 mutations. Subsequently, the result of Gene Ontology (GO) analysis showed that the mutated genes in this case were involved in neuron development. All of these findings indicated the diagnosis of DCS with neurogenic differentiation. Postoperatively, the patient received high-dose radiotherapy (60 Gy) and chemotherapy. There was no MRI evidence of tumor recurrence at the 21-month postoperative follow-up. Conclusions This unusual DCS case with neuronal differentiation is an important addition to the immuno-phenotypic spectrum of DCS. Although the prognosis for DCS is poor, gross tumor resection with high dose radiotherapy and chemotherapy may assist in prolonging survival.

الإتاحة: https://doi.org/10.1186/s13000-022-01252-1Test

المؤلفون: Hu, Yue, Zhang, Huawei, Adilijiang, Aihemaitiniyazi, Zhou, Jian, Guan, Yuguang, Qi, Xueling, Wang, Mengyang, Wang, Jing, Wang, Xiongfei, Liu, Changqing, Luan, Guoming

المساهمون: Scientific Research Common Program of Beijing Municipal Commission of Education, National Key R&D Program of China, Capital's Funds for Health Improvement and Research

المصدر: Frontiers in Surgery ; volume 9 ; ISSN 2296-875X

مصطلحات موضوعية: Surgery

الوصف: Introduction Ganglioglioma (GG) patients often present with seizures. Although most patients can be seizure-free after tumor resection, some still experience seizures. The present study aimed to analyze a group of GGs patients associated with epilepsy and evaluate the seizure outcomes and prognostic factors. Methods This retrospective study involved clinical data collected from medical records of patients diagnosed with GG pathologically and underwent surgical resection in Sanbo Brain Hospital, Capital Medical University. The seizure outcomes were evaluated based on the International League Against Epilepsy (ILAE) seizure outcome classification. The prognostic factors were identified according to univariate and multivariate analysis. Results A total of 222 patients were included, with a mean age at surgery of 19.19 ± 10.93 years. All patients were followed up at least for one year with a mean follow-up duration of 6.28 ± 3.17 years. At the final follow-up, 174 (78.4%) patients achieved ILAE Class 1 or 2. Univariate and multivariate analyses revealed that the short duration of seizures and gross total resection were significant positive factors for seizure-free. Bilateral interictal or ictal epileptiform discharges in preoperative video-electroencephalogram (VEEG) were related to poor seizure outcomes. Conclusion Surgical resection is an effective treatment for patients with epilepsy associated with GGs. The analysis of predictive factors could effectively guide clinical practice and evaluate the prognosis of epilepsy with GG.

الإتاحة: https://doi.org/10.3389/fsurg.2022.946201Test

المؤلفون: Duan, Zejun, Yao, Kun, Yang, Shaomin, Qu, Yanming, Ren, Ming, Zhang, Yongli, Fan, Tao, Zhao, Heqian, Gao, Jie, Feng, Jing, Fan, Xiaolong, Qi, Xueling

المصدر: Modern Pathology ; volume 35, issue 12, page 1910-1920 ; ISSN 0893-3952

مصطلحات موضوعية: Pathology and Forensic Medicine

الإتاحة: https://doi.org/10.1038/s41379-022-01127-2Test
https://www.nature.com/articles/s41379-022-01127-2.pdfTest
https://www.nature.com/articles/s41379-022-01127-2Test
https://api.elsevier.com/content/article/PII:S089339522205503X?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S089339522205503X?httpAccept=text/plainTest