Therapeutic radiation drives leptomeningeal dissemination of medulloblastoma [scRNA-seq]
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ABSTRACT:
PROVIDER: PRJNA1105605 | ENA |
REPOSITORIES: ENA
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Project description:Therapeutic radiation drives leptomeningeal dissemination of medulloblastoma [bulkRNA-seq]
| PRJNA1105606 | ENA
Project description:In this study, we examine the effect of radiation on the transcriptional profile of medulloblastoma tumor cells and its microenvironment that could potentially be leading to metastatic dissemination.
2024-05-06 | GSE266048 | GEO
Project description:In this study, we examine the effect of radiation on the transcriptional profile of medulloblastoma tumor cells and its microenvironment that could potentially be leading to metastatic dissemination.
2024-05-06 | GSE266047 | GEO
Project description:The main cause of death in medulloblastoma is recurrence associated with leptomeningeal dissemination. Although the molecular basis of medulloblastoma has received considerable attention over the past decade, the role of microRNAs (miRNAs) in the acquisition of metastatic phenotype remains poorly understood. This study aimed to identify miRNA involved in leptomeningeal dissemination and to elucidate its target mechanisms. We analyzed miRNA expression profiles of 29 medulloblastomas according to the presence of cerebrospinal fluid (CSF) seeding. The differential expressed miRNAs (DEmiRNAs) were validated on 29 medulloblastoma tissues and three medulloblastoma cells. The biological function of the selected miRNA was evaluated using in vitro studies. A total of 12 DEmiRNAs were identified including miRNA-192 in medulloblastoma with seeding. The reduced expression of miRNA-192 was confirmed in tumor seeding group and the medulloblastoma cells. Overexpression of miRNA-192 inhibited cellular proliferation targeting dihydrofolate reductase (DHFR). MiRNA-192 decreased cellular anchoring via repression of integrin subunits (αV, β1, and β3) and CD47. Medulloblastoma with seeding showed specific DEmiRNAs compared with those without seeding. MicroRNA-192 suppresses leptomeningeal dissemination of medulloblastoma through modulating cell proliferation and anchoring ability. leptomeningeal dissemination in 29 pediatric medulloblastoma patients
2015-12-31 | E-GEOD-66968 | biostudies-arrayexpress
Project description:The main cause of death in medulloblastoma is recurrence associated with leptomeningeal dissemination. Although the molecular basis of medulloblastoma has received considerable attention over the past decade, the role of microRNAs (miRNAs) in the acquisition of metastatic phenotype remains poorly understood. This study aimed to identify miRNA involved in leptomeningeal dissemination and to elucidate its target mechanisms. We analyzed miRNA expression profiles of 29 medulloblastomas according to the presence of cerebrospinal fluid (CSF) seeding. The differential expressed miRNAs (DEmiRNAs) were validated on 29 medulloblastoma tissues and three medulloblastoma cells. The biological function of the selected miRNA was evaluated using in vitro studies. A total of 12 DEmiRNAs were identified including miRNA-192 in medulloblastoma with seeding. The reduced expression of miRNA-192 was confirmed in tumor seeding group and the medulloblastoma cells. Overexpression of miRNA-192 inhibited cellular proliferation targeting dihydrofolate reductase (DHFR). MiRNA-192 decreased cellular anchoring via repression of integrin subunits (αV, β1, and β3) and CD47. Medulloblastoma with seeding showed specific DEmiRNAs compared with those without seeding. MicroRNA-192 suppresses leptomeningeal dissemination of medulloblastoma through modulating cell proliferation and anchoring ability.
2015-12-31 | GSE66968 | GEO
Project description:Herein we describe a case with histological, immunohistochemical and molecular features of GTAKA showing widespread leptomeningeal dissemination.
2024-07-17 | GSE253610 | GEO
Project description:Herein we describe a case with histological, immunohistochemical and molecular features of GTAKA showing widespread leptomeningeal dissemination.
2024-07-17 | GSE253604 | GEO
Project description:This case shows similarities with 2 previously reported cases, including intraventricular location, histologic appearance (pushing borders, oligodendrocyte-like morphology, rich vascular network) and immunophenotype with co-expression of OLIG2, GFAP and synaptophysin. The onset in an infant, the presence of a high-grade component and the leptomeningeal dissemination, however, have not been previously reported in EWSR1-PATZ1 rearranged tumors, expanding the clinico-pathological spectrum.
2020-12-03 | GSE162537 | GEO
Project description:Aberrant oncogenic activation of MYC drives tumorigenesis in the most aggressive subset of medulloblastoma, the most common malignant brain tumor in childhood. Metastatic dissemination at diagnosis and at recurrence is commonly observed in MYC-driven medulloblastomas. Since these tumors display remarkable resistance to standard multimodal therapeutic approaches, epigenetic modulators commonly altered in these tumors are highly promising targets for novel therapeutic approaches. Here, we report on a cross-entity, high-throughput epigenetic drug screen to evaluate therapeutic vulnerabilities in the most common malignant primary brain tumors. Specifically, we performed a primary screen including 78 epigenetic inhibitors and a secondary screen including 20 histone deacetylase inhibitors (HDACi) to compare response profiles in atypical teratoid/rhabdoid tumor (AT/RT, n=11), medulloblastoma (n=14), and glioblastoma (n=14). This unbiased approach revealed preferential activity of HDACi in MYC-driven medulloblastoma. Importantly, the class I selective HDACi CI-994 showed significant cell viability reduction mediated by induction of apoptosis in MYC-driven medulloblastoma, with little to no activity in non-MYC-driven medulloblastoma, AT/RT, and glioblastoma in vitro. Notably, CI-994 displayed antitumoral effects at the primary site and the metastatic compartment in two orthotopic mouse models of MYC-driven medulloblastoma. Furthermore, synergistic drug screening and RNA sequencing revealed NFκB pathway induction as a mechanism of resistance to CI-994 treatment. Taken together, our findings identified MYC pathway activation as a predictive biomarker for epigenetic treatment intervention in high-risk medulloblastoma and provide a preclinical rationale for further exploration of CI-994 combined with NFκB pathway inhibitors in the treatment of MYC-driven medulloblastoma.
2019-12-13 | GSE123760 | GEO
Project description:Medulloblastoma is the most common malignant pediatric brain tumor, and leptomeningeal dissemination (LMD) of medulloblastoma portends a poorer prognosis at diagnosis and is incurable at recurrence. The biological mechanisms underlying LMD in medulloblastoma are largely unclear. The Abelson (ABL) family of non-receptor tyrosine kinases has been implicated in cancer cell migration, invasion, adhesion, and chemotherapy resistance, and these kinases are upstream mediators of the oncogene c-MYC in fibroblasts. However, their role in medulloblastoma has not yet been explored. Therefore, the purpose of this work is to elucidate the role of the ABL kinases, ABL1 and ABL2, in medulloblastoma LMD. We show here that ABL1/2 mRNA is highly expressed in human medulloblastoma tumor samples and cell lines and that pharmacologic inhibition of ABL kinases results in medulloblastoma cell death. Knockdown of the ABL kinase genes ABL1 and ABL2 results in decreased adhesion to the extracellular matrix protein, vitronectin, and decreased medulloblastoma proliferation in a mouse model of medulloblastoma LMD (resulting in decreased tumor burden with subsequent increased overall survival. Further, both pharmacologic inhibition of ABL1/2 and ABL1/2 knockdown resulted in decreased c-myc expression, revealing a putative signaling pathway. In summary, this work highlights the potential role of ABL kinases in medulloblastoma LMD via c-myc expression.
2023-10-04 | GSE224691 | GEO