GEO DataSets

(Submitter supplied) We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC gene family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this molecular group died of rapidly progressive disease post-relapse. To study this genetic interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. more...

Organism:

Homo sapiens

Type:

Methylation profiling by genome tiling array

Platform:

GPL13534

40 Samples

Download data: CSV

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by array; Genome variation profiling by genome tiling array

Platforms:

GPL6885 GPL13534

88 Samples

Download data: IDAT

(Submitter supplied) We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC gene family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this molecular group died of rapidly progressive disease post-relapse. To study this genetic interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6885

48 Samples

Download data: IDAT, TXT

(Submitter supplied) Smoothened (SMO)-inhibitors recently entered clinical trials for sonic-hedgehog driven medulloblastoma (SHH-MB). Clinical response appears highly variable. To understand the mechanism(s) of primary resistance and to identify pathways co-operating with aberrant SHH-signaling, we sequenced a large cohort of SHH-MBs across all age groups by sequencing, DNA methylation and expression profiling. Our data show that most adults but only half of the pediatric patients with SHH-MB will respond to SMO inhibition as predicted by molecular analysis of the primary tumor and tested in the SHH-xenografts, demonstrating that the next generation of SMO-inhibitor trials should be based on these predictive biomarkers. more...

Organism:

Homo sapiens

Type:

Methylation profiling by array

Platform:

GPL13534

83 Samples

Download data: TXT

(Submitter supplied) Smoothened (SMO)-inhibitors recently entered clinical trials for sonic-hedgehog driven medulloblastoma (SHH-MB). Clinical response appears highly variable. To understand the mechanism(s) of primary resistance and to identify pathways co-operating with aberrant SHH-signaling, we sequenced a large cohort of SHH-MBs across all age groups by sequencing, DNA methylation and expression profiling. Our data show that most adults but only half of the pediatric patients with SHH-MB will respond to SMO inhibition as predicted by molecular analysis of the primary tumor and tested in the SHH-xenografts, demonstrating that the next generation of SMO-inhibitor trials should be based on these predictive biomarkers. more...

Organism:

Homo sapiens

Type:

Methylation profiling by genome tiling array

Platform:

GPL13534

46 Samples

Download data: TXT

(Submitter supplied) Smoothened (SMO)-inhibitors recently entered clinical trials for sonic-hedgehog driven medulloblastoma (SHH-MB). Clinical response appears highly variable. To understand the mechanism(s) of primary resistance and to identify pathways co-operating with aberrant SHH-signaling, we sequenced a large cohort of SHH-MBs across all age groups by sequencing, DNA methylation and expression profiling. Our data show that most adults but only half of the pediatric patients with SHH-MB will respond to SMO inhibition as predicted by molecular analysis of the primary tumor and tested in the SHH-xenografts, demonstrating that the next generation of SMO-inhibitor trials should be based on these predictive biomarkers. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

73 Samples

Download data: CEL

(Submitter supplied) Identification of novel molecular subgroups Background: International consensus recognises four medulloblastoma molecular subgroups - WNT, SHH, Group 3 and Group 4 - each defined by their characteristic genome-wide transcriptomic and DNA methylomic profiles. Subgroups harbor distinct clinico-pathological and molecular features, underpin current disease sub-classification and initial subgroup-directed therapies are underway in clinical trials (i.e. more...

Organism:

Homo sapiens

Type:

Methylation profiling by genome tiling array

Platform:

GPL13534

428 Samples

Download data: IDAT, TXT

(Submitter supplied) BACKGROUND Focal high-level amplifications of MYC define a subset of high-risk medulloblastoma patients. However, the prognostic role of MYCN oncogene amplification remains less clear. We aimed to evaluate the prognostic value of this alteration alone and in combination with biological modifiers in a large cohort of 67 pediatric medulloblastomas with MYCN amplification (MYCN-MB). METHODS Twenty-one MYCN-MB with MYCN amplication and 56 MYCN-MB were respectively examined using either gene expression profiling and array-CGH, or immunohistochemical analysis and FISH. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6480

77 Samples

Download data: TXT

(Submitter supplied) Pediatric medulloblastoma is considered a highly heterogeneous disease, and a new strategy of risk stratification to optimize therapeutic outcomes is required. We aimed to investigate a new risk-stratification approach based on expression profiles of medulloblastoma cohorts. We analyzed gene expression profiles of 30 primary medulloblastomas and detected strong evidence that poor survival outcome was significantly associated with mRNA expression profiles of 17p loss. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

30 Samples

Download data: CEL

(Submitter supplied) Human neural stem and progenitor cells transformed with c-MYC, dominant-negative p53, constitutively active AKT and hTERT formed tumors in mice that recapitulated Group 3 medulloblastoma in terms of pathology and expression profile

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL13158

6 Samples

Download data: CEL

(Submitter supplied) DNA copy-number profiling of 80 primary medulloblastomas of different histologies Keywords: Genetic modification

Organism:

Homo sapiens

Type:

Genome variation profiling by genome tiling array

Platform:

GPL5685

80 Samples

Download data: GPR

(Submitter supplied) Tumor recurrence is a slow biological process involving therapy resistance, immune escape and metastasis and is the leading cause of death in medulloblastoma, the most frequent malignant pediatric brain tumor. By studying paired primary-recurrent patient samples and patient-derived xenografts we identified significant accumulation of SOX9-positive cells in relapses and metastases. They exist as rare, quiescent cells in Group 3 and Group 4 patients that constitute two thirds of medulloblastoma. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL16331 GPL24247

44 Samples

Download data: TXT

(Submitter supplied) Group 3 medulloblastoma (MB) carries the worst prognosis of the four molecular subgroups of MB. MYC amplifications represent the most common genetic alteration in Group 3 MB. By specifically driving MYC in hindbrain cells using a Tet-OFF system, we established a novel murine model of MB (GMYC) that accurately recapitulates human Group 3 MB. GMYC tumours develop with 60-70% penetrance, without p53 mutations, and are monoclonal as revealed by multicolour cell fate tracing. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL27583 GPL16331

32 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Expression profiling by array

Platforms:

GPL11180 GPL1261

79 Samples

Download data: CEL

(Submitter supplied) A series of mouse models designed to mimic pediatric medulloblastoma types in humans were tested by microarray and compared to published human medulloblastoma data

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL11180

15 Samples

Download data: CEL

(Submitter supplied) Mouse models of medulloblastoma are compared to human subgroups through microarray expression and other measures

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

64 Samples

Download data: CEL

(Submitter supplied) Group 3 medulloblastoma is often associated with MYC amplification or overexpression, while whether MYC overexpression alone is sufficient to induce tumorigenesis is unknown and the cell type(s) which can be transformed by MYC is unclear. Here, by generating a new mouse model, we demonstrated that overexpression of Myc alone is sufficient to transform astrocyte progenitors and granule neuron progenitors (GNP) in the early postnatal cerebellum following orthotopic transplantation. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21103

21 Samples

Download data: TXT

(Submitter supplied) MYC genes are frequently amplified and correlate with poor prognosis in MB. BET bromodomains recognize acetylated lysine residues and often promote and maintain MYC transcription. Certain cyclin-dependent kinases (CDKs) are further known to support MYC stabilization in tumor cells. In this report, MB cells were suppressed by combined targeting of MYC expression and MYC stabilization using BET bromodomain inhibition and CDK2 inhibition, respectively. more...

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL17301 GPL16331

50 Samples

Download data: TSV

(Submitter supplied) 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. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Dataset:

GDS4478

Platform:

GPL1261

19 Samples

Download data: CEL

Analysis of Myc/DNp53-infected tumors derived from stem cells or progenitors, uninfected stem cells, and patched tumor cells. Cerebellar stem cells expressing Myc and mutant Trp53 generate tumors similar to MYC-driven medulloblastoma (MB). Results provide insight into transformation to MB tumor.

Organism:

Mus musculus

Type:

Expression profiling by array, transformed count, 4 cell type, 3 genotype/variation, 4 other sets

Platform:

GPL1261

Series:

GSE34126

19 Samples

Download data: CEL