Filters
Technology
Platform
Mus musculus
17 Downloadable Samples
Description
Medulloblastoma (MB) is the most common malignant brain tumor in children. Patients whose tumors exhibit overexpression or amplification of the MYC oncogene (c-MYC) usually have an extremely poor prognosis, but there are no animal models of this subtype of the disease. Here we show that cerebellar stem cells expressing Myc and mutant Trp53 (p53) generate aggressive tumors following orthotopic transplantation. These tumors consist of large, pleiomorphic cells and resemble human MYC-driven MB at a molecular level. Notably, antagonists of PI3K/mTOR signaling, but not Hedgehog signaling, inhibit growth of tumor cells. These findings suggest that cerebellar stem cells can give rise to MYC-driven MB, and identify a novel model that can be used to test therapies for this devastating disease.
Publication Title
An animal model of MYC-driven medulloblastoma.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 64 Downloadable Samples
Description
Mouse models of medulloblastoma are compared to human subgroups through microarray expression and other measures
Publication Title
A mouse model of the most aggressive subgroup of human medulloblastoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 27 Downloadable Samples
Description
Origins of the brain tumor, medulloblastoma, from stem cells or restricted pro-genitor cells are unclear. To investigate this, we activated oncogenic Hedgehog signaling in multipotent and lineage-restricted CNS progenitors. We observed that normal unipo-tent cerebellar granule neuron precursors (CGNP) derive from hGFAP+ and Olig2+ rhombic lip progenitors. Hedgehog activation in a spectrum of early and late stage CNS progenitors generated similar medulloblastomas, but not other brain cancers, indicating that acquisition of CGNP identity is essential for tumorigenesis. We show in human and mouse medulloblastoma that cells expressing the glia-associated markers Gfap and Olig2 are neoplastic and that they retain features of embryonic-type granule lineage progenitors. Thus, oncogenic Hedgehog signaling promotes medulloblastoma from lineage-restricted granule cell progenitors.
Publication Title
Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 285 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Affymetrix Human Gene 1.1 ST Array profiling of 285 primary medulloblastoma samples.
Publication Title
Subgroup-specific structural variation across 1,000 medulloblastoma genomes.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 12 Downloadable Samples
Description
The main cell of origin of the Sonic hedgehog (SHH) subgroup of medulloblastoma (MB) is granule cell precursors (GCPs), a SHH-dependent transient amplifying population in the developing cerebellum. SHH-MBs can be further subdivided based on molecular and clinical parameters, as well as location since SHH-MBs occur preferentially in the lateral cerebellum (hemispheres). Our analysis of adult patient data suggests that tumors with Smoothened (SMO) mutations form more specifically in the hemispheres than those with Patched 1 (PTCH1) mutations. Using sporadic mouse models of SHH-MB with the two mutations commonly seen in adult MB, constitutive activation of Smo (SmoM2) or loss-of-Ptch1, we found that regardless of timing of induction or type of mutation, tumors developed primarily in the hemispheres with SmoM2-mutants indeed showing a stronger specificity. We further uncovered that GCPs in the hemispheres are more susceptible to high level SHH signaling compared to GCPs in the medial cerebellum (vermis), as more SmoM2 or Ptch1-mutant hemisphere cells remain undifferentiated and show increased tumorigenicity when transplanted. Finally, we identified location-specific GCP gene expression profiles, and found that deletion of the genes most highly expressed in the hemispheres (Nr2f2) or vermis (Engrailed1) showed opposing effects on GCP differentiation. Our studies thus provide new insights into intrinsic differences within GCPs that impact on SHH-MB progression.
Publication Title
Lateral cerebellum is preferentially sensitive to high sonic hedgehog signaling and medulloblastoma formation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 64 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A mouse model of the most aggressive subgroup of human medulloblastoma.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 17 Downloadable Samples
Description
Objective: Otitis media is known to alter expression of cytokine and other genes in the mouse middle ear and inner ear. However, whole mouse genome studies of gene expression in otitis media have not previously been undertaken. Ninety-nine percent of mouse genes are shared in the human, so these studies are relevant to the human condition.
Publication Title
Otitis media impacts hundreds of mouse middle and inner ear genes.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples
GSE49122- Mus musculus
- 13 Downloadable Samples
Description
Objective: Otitis media is known to alter expression of cytokine and other genes in the mouse middle ear and inner ear. However, whole mouse genome studies of gene expression in otitis media have not previously been undertaken. Ninety-nine percent of mouse genes are shared in the human, so these studies are relevant to the human condition.
Publication Title
Otitis media impacts hundreds of mouse middle and inner ear genes.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 23 Downloadable Samples
Description
Nude mice were allografted with medulloblastoma tumors derived from Ptch+/-HIC+/- transgenic mouse and treated with vehicle or NVP-LDE225.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 19 Downloadable Samples
Description
Nude mice were allografted with medulloblastoma tumors derived from Ptch+/-p53-/- transgenic mouse and treated with vehicle or NVP-LDE225.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Treatment
View Samples