Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1206427 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Medulloblastoma (MB), the most common malignant pediatric brain tumor, comprises of four molecularly and clinically distinct subgroups (termed WNT, SHH, Group3, and Group4). Prognosis varies based on genetic and pathological features associated with each molecular subgroup. WNT-MB, considered low-risk, are rarely metastatic and contain activating mutations in CTNNB1; Group3-MB, commonly classified as high-risk, are frequently metastatic and can contain genomic alterations resulting in elevated MYC expression. Here we compare model systems of low-risk WNT-MB to high-risk Group3-MB to identify tumor and microenvironment interactions that could contribute to features associated with poor outcome. Compared to Group3-MB, we find that WNT-MB display enrichment in gene sets related to extracellular matrix (ECM) regulation and cellular adhesion. Exogenous expression of MycT58A in murine WNT-MB models significantly accelerates growth and results in metastatic disease. In addition to down-regulation of ECM regulation and cell adhesion pathways, we also identified immune system interactions among the top down-regulated signaling pathways following MycT58A expression. Taken together, our data provides evidence that increased Myc signaling can promote the growth and metastasis of WNT-MB.
2024-04-30 | GSE227631 | GEO
Project description:Group3 Medulloblastoma is a highly malignant pediatric brain tumor and despite patients harboring different genetic alterations they are treated with similar therapies. Here, we perform an in-vivo Patient-Specific screen and we identify Otx2 and c-Myc as strong inducers of Group3 Medulloblastoma. We demonstrate that the chromatin modifier Smarca4, also mutated in human patients, is able to reduce Otx2/c-Myc tumorigenic activity in-vivo. Furthermore, Otx2/c-Myc co-overexpression in human cerebellar organoids generates Medulloblastoma-like organoids that induce brain cancer in mice with a DNA methylation signature similar to human Group3 MB. Finally, inhibition of histone methyltransferases reduces Otx2/c-Myc tumorigenesis in ex-vivo culture and in human cerebellar organoids. Therefore, understanding the role of different altered genes in Medulloblastoma patients will be of great importance to develop new personalized therapies.
2020-03-01 | GSE128218 | GEO
Project description:We examined the transformation susceptibility of different cerebellar stem/progenitors by developing several new Group3 medulloblastoma murine models using orthotopic transplantation and in utero electroporation (EP)-based in vivo gene transfer with Cre/LoxP-mediated conditional Myc gene activation and loss of Trp53 function. We used microarrays to compared the transcriptome of these novel Group3 medulloblastoma mouse models and CPC mouse models to existing mouse models of medulloblastoma subgroups and used cross-species analysis to compare these models to human medulloblastoma subgroups
2015-02-13 | GSE65888 | GEO
Project description:We undertook a meta-analysis based on DNA methylation patterns of Group3/4 subgroup medulloblastoma from three published studies, alongside additional unpublished tumours (total n=1501).
2019-06-11 | GSE130051 | GEO
Project description:Objectives: To identify gene expression changes in acne flare-up patients, thereby exploring the mechanisms of acne flare-up after treatment. Methods: 11 acne patients and 3 healthy people were divided into 4 groups (group1: 4 with flare-up, group2: 4 with improvement, group3: 3 without obvious changes, group4: healthy control). Peripheral blood of patients before and after isotretinoin or minocycline were collected. RNA-seq were used to detect the gene expression. We applied data in self-contrast and intergroup comparisons. Results: In the self-contrast of group1, 22 upregulated genes were involved in Toll-like receptor signaling pathway and inflammatory response. Comparing group1 and group3 before treatment, 1778 upregulated genes enriched in Th17 cell differentiation, while 57 downregulated genes enriched in defensive response to organism. Conclusions: The gene expression profiles of acne flare-up patients changed. Inflammatory, immune responses played a prominent role in acne flare-up process and relatively weak defensive response to microbes, comedogenesis might be risk factors.
2018-12-27 | GSE124389 | GEO
Project description:We devised a high-throughput, cell-based assay to identify novel therapeutic compounds to treat Group3 medulloblastoma (G3 MB). Mouse G3 MBs, grown as neurospheres, were screened against a library of approximately 7,000 compounds including FDA-approved drugs. We identified two FDA-approved drugs, pemetrexed and gemcitabine that preferentially inhibited tumor proliferation in vitro compared to control neurospheres, and substantially inhibited tumor proliferation in vivo. When combined, the two drugs significantly increased survival
2014-04-15 | GSE46406 | GEO