GEO DataSets

(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) 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) 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) Cancer stem cells (CSCs) play major roles in cancer initiation, progression, and metastasis. It is evident from growing reports that PI3K/Akt/mTOR and Sonic Hedgehog (Shh) signaling pathway are aberrantly reactivated in pancreatic CSCs. Here, we examined the efficacy of combining NVP-LDE-225 (PI3K/mTOR inhibitor) and NVP-BEZ-235 (Smoothened inhibitor) on pancreatic CSCs characteristics, microRNA regulatory network, and tumor growth. more...

Organism:

Homo sapiens; synthetic construct

Type:

Non-coding RNA profiling by array

Platform:

GPL16384

8 Samples

Download data: CEL

(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) Medulloblastoma is the most common malignant pediatric brain tumor, and mechanisms underlying its development are poorly understood. We identified recurrent amplification of the miR-17/92 polycistron proto-oncogene in 6% of pediatric medulloblastomas by high-resolution single-nucleotide polymorphism genotyping arrays and subsequent interphase fluorescence in situ hybridization on a human medulloblastoma tissue microarray. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL5175

90 Samples

Download data: CEL

(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) Overactivation of the Hedgehog (HH) signaling pathway is implicated in many cancers. In this study, we demonstrate that the small molecule RITA, a p53 activator, effectively downregulates HH signaling in human medulloblastoma and rhabdomyosarcoma cells irrespective of p53. This is mediated by a ROS-independent activation of the MAP kinase JNK. We also show that in vitro RITA sensitized cells to the GLI antagonist GANT61, as co-administration of the two drugs had more pronounced effects on cell proliferation and apoptosis. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21697

16 Samples

Download data: TXT

(Submitter supplied) Affymetrix Human Gene 1.1 ST Array profiling of 83 primary SHH-driven medulloblastoma samples.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL11532

83 Samples

Download data: CEL, CHP

(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

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

Organism:

Mus musculus

Type:

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

Platforms:

GPL9185 GPL6887

33 Samples

Download data: TXT

(Submitter supplied) We report findings that illuminate a dynamic metastasis pathway in the common pediatric brain tumor medulloblastoma.

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL9185

12 Samples

Download data: BIGWIG

(Submitter supplied) We report findings that illuminate a dynamic metastasis pathway in the common pediatric brain tumor medulloblastoma.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL9185

9 Samples

Download data: TXT

(Submitter supplied) We report findings that illuminate a dynamic metastasis pathway in the common pediatric brain tumor medulloblastoma.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6887

12 Samples

Download data: TXT

(Submitter supplied) Cerebellar development requires regulated proliferation of cerebellar granule neuron progenitors (CGNPs). Inadequate CGNP proliferation causes cerebellar hypoplasia while excessive CGNP proliferation can cause medulloblastoma, the most common malignant pediatric brain tumor. Although Sonic Hedgehog (SHH) signaling is known to activate CGNP proliferation, the mechanisms down-regulating proliferation are less defined. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL17400

15 Samples

Download data: CEL

(Submitter supplied) To investigate Pten function in neonatal developing brain, we conditionally inactivated Pten in neural stem/progenitor cells at birth using a Nestin-CreER transgenic driver. Pten inactivation created a novel perivascular proliferative niche in the cerebellum that did not progress to malignancy during the lifespan of the mouse. Co-deletion of Pten and Trp53 synergized to cause fully penetrant medulloblastoma originating from a perivascular niche. more...

Organism:

Mus musculus

Type:

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

Platforms:

GPL1261 GPL4714

33 Samples

Download data: CEL, GPR

(Submitter supplied) We are examining the genes that control initiation and progression of murine medulloblastomas that result from loss of patched. Approximately 25% of human medulloblastomas have mutations in patched or in other elements of the sonic hedgehog pathway. However, the cells from which these tumors originate (neural progenitors or stem cells), the cells that are responsible for tumor propagation (cancer stem cells), and the genes that are required for tumor progression are poorly understood. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

21 Samples

Download data: CEL

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

Organism:

Mus musculus

Type:

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

Platform:

GPL17021

4 Samples

Download data: BED, TXT