A mouse model of the most aggressive subgroup of human medulloblastoma [Mouse430_2]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE33199 | GEO | 2012/02/29
SECONDARY ACCESSION(S): PRJNA156633
REPOSITORIES: GEO
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Project description:Mouse models of medulloblastoma are compared to human subgroups through microarray expression and other measures This study contrasts mouse medullablastomas from a range of mouse genetic models. For Shh-type medulloblastoma [dka001-005, 009, 033 and 034] and [dka050-057], spontaneous medulloblastomas from [Cdkn2c-/-; Trp53Fl/Fl; Nestin-Cre] and [Cdkn2c-/-; Ptch1+/-] (Uziel et al.,2005 Genes Dev) were used, respectively. For Myc [dka010-022, 037, 046, 049 and 058-71] and Mycn [dka023-032, 036 and 047] were generated by orthotopic injection of either Myc or Mycn overexpression in Cdkn2c-/-, Trp53-/- cerebellar cells into immunocompromised nude mice. For Wnt-type medulloblastomas [pgr003, 016 and 066], spontaneously developed tumors from CTNNB1+/lox (ex3); BLBP-Cre; Trp53Fl/Fl (Gibson et al., Nature, 2010) were removed for RNA extraction.
2012-02-29 | E-GEOD-33199 | biostudies-arrayexpress
Project description:A series of mouse models designed to mimic pediatric medulloblastoma types in humans were tested by microarray and compared to published human medulloblastoma data
2012-02-29 | GSE33200 | GEO
Project description:A series of mouse models designed to mimic pediatric medulloblastoma types in humans were tested by microarray and compared to published human medulloblastoma data Myc-type tumors [dka201-203] were generated by orthotopic injection of Myc-infected cerebellar cells from Cdkn2c-/-, Trp53-/-, Atoh1-GFP mice into the cerebral cortex of immunocompromised nude mice. For Shh-type medulloblastomas [dka204-206], spontaneous medulloblastomas from [Cdkn2c-/-; Trp53Fl/Fl; Nestin-Cre] (Uziel et al.,2005 Genes Dev) were used. FACS-sorted GFP-positive [dka220-222] and GFP-negative [dka211, 212 and 219] populations were obtained from postnatal day 6 Cdkn2c-/-, Trp53-/-, Atoh1-GFP cerebella. Myc-type secondary tumors [dka223-225] were generated by orthotopic transplantation of cultured sphere cells from Myc-type primary tumors.
2012-02-29 | E-GEOD-33200 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE33199: A mouse model of the most aggressive subgroup of human medulloblastoma [Mouse430_2] GSE33200: A mouse model of the most aggressive subgroup of human medulloblastoma [HT_MG-430_PM] Refer to individual Series
2012-02-29 | E-GEOD-33201 | biostudies-arrayexpress
Project description:Medulloblastomas that display a large cell/anaplastic morphology and overexpress the cellular c-MYC gene are highly aggressive and carry a very poor prognosis. This so-called MYC-subgroup differs in its histopathology, gene expression profile, and clinical behavior from other forms of medulloblastoma. We generated a mouse model of MYC-subgroup medulloblastoma by transducing Trp53-null cerebellar progenitor cells with Myc. The cardinal features of these mouse medulloblastomas closely mimic those of human MYC-subgroup tumors and significantly differ from mouse models of the Sonic-Hedgehog- and WNT-disease subgroups. This mouse model should significantly accelerate understanding and treatment of the most aggressive form of medulloblastoma and infers distinct roles for MYC and MYCN in tumorigenesis.
| S-EPMC3285412 | biostudies-literature
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: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:This SuperSeries is composed of the SubSeries listed below.
2012-02-29 | GSE33201 | GEO
Project description:In order to investigate medulloblastoma biology via its proteome, we undertook a super-SILAC quantitative proteomics survey using 41 clinical tissue samples spanning the 4 genomic subgroups and control cerebellum
2018-06-10 | PXD008750 | Pride
Project description:We explore cellular heterogeneity in 28 childhood medulloblastoma (MB) (1 WNT, 9 SHH, 7 GP3 and 11 GP4) using single-cell RNA sequencing (scRNA-seq), immunohistochemistry and deconvolution of bulk transcriptomic data. Neoplastic cells are broadly clustered according to subgroup, and within subgroups discrete sample clustering is associated with chromosomal copy number variance. Each subgroup contains subpopulations exhibiting mitotic , undifferentiated and neuronal differentiated transcript profiles , corroborating other recent medulloblastoma scRNA-seq studies and identifying new subpopulations. We identify a photoreceptor-differentiated subpopulation that is predominantly found in GP3 medulloblastoma, and in SHH, a subpopulation that constitutes differentiating nodules . Deconvolution of a large transcriptomic dataset shows that neoplastic subpopulations are associated with major and minor subgroup subdivisions, for example, photoreceptor subpopulation cells are more abundant in GP3-alpha. This scRNA-seq dataset also demonstrates medulloblastoma subgroup-specific differences in the tumor microenvironment and immune landscape, and reveals an SHH nodule -associated myeloid subpopulation. Additionally, we perform scRNA-seq on genetically engineered mouse (GEM) models of GP3 and SHH medulloblastoma. These models specifically matched the corresponding human subgroup-specific neoplastic subpopulations. We provide an interactive online resource that facilitates exploration of these MB single cell datasets. Collectively, our findings advance our understanding of the neoplastic and immune landscape of the main medulloblastoma subgroups in both humans and GEM models.
2021-06-04 | GSE155446 | GEO