GEO DataSets

(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:

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:

Expression profiling by array

Platform:

GPL570

73 Samples

Download data: CEL

(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) 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) Here we performed a targeted small molecule screen on a stable, SHH-dependent murine MB cell line (SMB21). A subset of the HDAC inhibitors tested significantly inhibit tumor growth of SMB21 cells by preventing SHH pathway activation. Of note, class I HDAC inhibitors were also efficacious in suppressing growth of diverse SMO inhibitor-resistant clones of SMB21 cells. Finally, we show that the novel HDAC inhibitor Quisinostat (JNJ) targets multiple class I HDACs, is well tolerated in mouse models and robustly inhibits growth of SHH MB cells in vivo as well as in vitro. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

21 Samples

Download data: TXT

(Submitter supplied) Mutations in Hedgehog (Hh) pathway genes, leading to constitutive activation of Smoothened (Smo), occur in sporadic medulloblastoma, the most common brain cancer in children. Antagonists of Smo induce tumor regression in mouse models of medulloblastoma and hold great promise for targeted therapy for this tumor. However, acquired resistance has emerged as one of the major challenges of targeted cancer therapy. more...

Organism:

Mus musculus

Type:

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

Platforms:

GPL4092 GPL1261

27 Samples

Download data: CEL, TXT

(Submitter supplied) Aberrant Shh signaling promotes tumor growth in diverse human cancers. The importance of Shh signaling is particularly evident in medulloblastoma and basal cell carcinoma (BCC), where inhibitors targeting the Shh pathway component Smoothened (Smo) show great therapeutic promise. However, the emergence of drug resistance limits long-term efficacy and the mechanisms of resistance remain poorly understood. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL8321

24 Samples

Download data: CEL

(Submitter supplied) The Sonic Hedgehog (Shh) pathway drives a subset of medulloblastomas, a malignant neuroectodermal brain cancer, and other cancers. Small-molecule Shh pathway inhibitors have induced tumor regression in mice and patients with medulloblastoma; however, drug resistance rapidly emerges, in some cases via de novo mutation of the drug target. Here we assess the response and resistance mechanisms to the natural product derivative saridegib in an aggressive Shh-driven mouse medulloblastoma model. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6887

6 Samples

Download data: TXT

(Submitter supplied) 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. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

12 Samples

Download data: CEL

(Submitter supplied) GLI2 overexpression is a hallmark in SHH subgroup of medulloblastoma (SHH MB). Here we profile the transcriptome of two mouse models of SHH MB expressing high Gli2: SmoM2 overexpression and Sufu;Spop double knockout MB.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

9 Samples

Download data: TXT

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

Organism:

Mus musculus

Type:

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

Platforms:

GPL17021 GPL6246

34 Samples

Download data: CEL, TXT

(Submitter supplied) GLI2 overexpression is a hallmark in SHH subgroup of medulloblastoma (SHH MB). Here we identify the targetome of Gli2 in two mouse models of SHH MB: SmoM2 overexpression and Sufu;Spop double knockout MB.

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL17021

16 Samples

Download data: BROADPEAK, NARROWPEAK

(Submitter supplied) SUFU alterations are commonly detected in human SHH subgroup of medulloblastoma. Here we profile the gene expression of P13 wildtype and Sufu KO cerebellum, as well as Ptch1 KO MB in biological triplicate.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6246

9 Samples

Download data: CEL

(Submitter supplied) Cellular diversity within tumors and reduced lineage commitment can undermine targeted therapy by increasing the probability of treatment-resistant populations. Using single-cell RNA-seq, we analyzed cellular diversity and lineage in medulloblastomas in transgenic, medulloblastoma-prone mice, and responses to the SHH-pathway inhibitor vismodegib.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21103

15 Samples

Download data: TXT

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

Organism:

Mus musculus; Homo sapiens

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) 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) Macrophages, play an essential role in promoting tumor growth by affecting angiogenesis, immune suppression, invasion and metastasis. The signal transduction events within macrophages which encode the complex cascade of events required for tumor growth and polarization of macrophages are poorly understood. We have discovered an ECM dependent signaling pathway in macrophages that regulates M2 macrophage differentiation, tumor growth, invasion and metastasis. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6246

12 Samples

Download data: CEL

(Submitter supplied) Only a minority of medulloblastoma cells can self-renew and sustain tumor growth. In the Patched1+/- mouse model, these cells are quiescent and express the stem cell marker Sox2. We sought to define the gene expression profiling of these cells to gain insight into the molecular pathways that govern this population. Sox2-expressing and Sox2-negative cells were isolated from primary Sox2-eGFP;Patched1+/- tumors as GFP+ or GFP- tumors, respectively.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL16570

8 Samples

Download data: CEL, CHP