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SRP106034
Homo sapiens
16 Downloadable Samples
Illumina HiSeq 2500
Description
The differential gene expression of human cardiomyocytes induced by kinase inhibitors sorafenib and sunitinib is measured by a high-throughput mRNA-sequencing approach called 3''-DGE, that is based on a 3'' end-focused reference sequence library and a transcript molecule counting method with unique molecular identifiers (UMI) for correcting PCR bias. Overall design: Cells were treated with sunitinib, sorafenib, or vehicle control for 48 hours, and gene expression levels of all samples were measured by 3''-DGE and conventional random-primed mRNA-sequencing methods using paired-end reading to obtain the genome-wide expression profiles for each sample.
Publication Title
A Comparison of mRNA Sequencing with Random Primed and 3'-Directed Libraries.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 30 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Whole genome sequencing detected structural rearrangements of TERT in 17/75 high stage neuroblastoma with 5 cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted immediate up- and down-stream regions of TERT, placing in 7 cases a super-enhancer close to the breakpoints. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high stage neuroblastoma, each associated with very poor prognosis
Publication Title
TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A NOTCH feed-forward loop drives reprogramming from adrenergic to mesenchymal state in neuroblastoma.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Homo sapiens
- 58 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To identify molecular subtypes of medulloblastoma we have profiled a series of 62 medulloblastoma tumors. Unsupervised hierarchical cluster analysis of these data identified 5 distinct molecular subtypes.
Publication Title
Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 48 Downloadable Samples
- Illumina HiSeq 2000
Description
Oligodendrocyte precursor cells (OPCs) constitute the main proliferative cells in the adult brain, and deregulation of OPC proliferation-differentiation balance results in either glioma formation or defective adaptive (re)myelination. OPC differentiation requires significant genetic reprogramming implicating chromatin remodeling. Mounting evidence indicates that chromatin remodelers play important roles during normal development and their mutations are associated with neurodevelopmental defects, with CHD7 haploinsuficiency being the cause of CHARGE syndrome and CHD8 being one of the strongest Autism Spectrum Disorder (ASD) high-risk associated genes. Here, we report on uncharacterized functions of the chromatin remodelers Chd7 and Chd8 in OPCs. Their OPC-chromatin-binding profile combined with transcriptome and chromatin accessibility analyses of Chd7-deleted OPCs, demonstrates that Chd7 protects non-proliferative OPCs from apoptosis by chromatin-closing and transcriptional repression of p53. Furthermore, Chd7 controls OPC differentiation through chromatin-opening and transcriptional activation of key regulators, including Sox10, Nkx2.2 and Gpr17. Chd7 is however dispensable for oligodendrocyte stage progression, consistent with Chd8 compensatory function, as suggested by their common chromatin binding profiles and genetic interaction. Finally, CHD7 and CHD8 bind in OPCs to a majority of ASD-risk associated genes, suggesting an implication of oligodendrocyte lineage cells in ASD neurological defects. Our results thus offer new avenues to understand and modulate the CHD7 and CHD8 functions in normal development and disease. Overall design: RNA-seq from Chd7iKO and Control O4+ soted cells
Publication Title
Oligodendrocyte precursor survival and differentiation requires chromatin remodeling by Chd7 and Chd8.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 205 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Ependymal tumors across age groups have been classified and graded solely by histopathology. It is, however, commonly accepted that this classification scheme has limited clinical utility based on its lack of reproducibility in predicting patient outcome. We aimed at establishing a reliable molecular classification using DNA methylation fingerprints and gene expression data of the tumors on a large cohort of 500 tumors. Nine robust molecular subgroups, three in each anatomic compartment of the central nervous system (CNS), were identified.
Publication Title
Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Inactivating mutations in SMARCA4 (BRG1), a key SWI/SNF chromatin remodelling gene, underlie small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). To reveal its druggable vulnerabilities, we perform kinase-focused RNAi screens and uncover that SMARCA4-deficient SCCOHT cells are highly sensitive to the inhibition of cyclin-dependent kinase 4/6 (CDK4/6). SMARCA4 loss causes profound downregulation of cyclin D1, which limits CDK4/6 kinase activity in SCCOHT cells and leads to in vitro and in vivo susceptibility to CDK4/6 inhibitors. SCCOHT patient tumors are deficient in cyclin D1 yet retain the retinoblastoma-proficient/p16INK4a-deficient profile associated with positive responses to CDK4/6 inhibitors. Thus, our findings indicate that CDK4/6 inhibitors, approved for a breast cancer subtype addicted to CDK4/6 activation, could be repurposed to treat SCCOHT. Moreover, our study suggests a novel paradigm whereby critically low oncogene levels, caused by loss of a driver tumor suppressor, may also be exploited therapeutically. Overall design: The effect of CDK6 knockdown and palbociclib treatment on SCCOHT cells.
Publication Title
CDK4/6 inhibitors target SMARCA4-determined cyclin D1 deficiency in hypercalcemic small cell carcinoma of the ovary.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 49 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigenetically analyzed a large series of human ATRTs. Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified. Whole-genome DNA and RNA sequencing found no recurrent mutations in addition to SMARCB1 that would explain the differences between subgroups. Whole-genome bisulfite sequencing and H3K27Ac chromatin-immunoprecipitation sequencing of primary tumors, however, revealed clear differences, leading to the identification of subgroup-specific regulatory networks and potential therapeutic targets.
Publication Title
Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 1 Downloadable Sample
- Illumina MouseRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Interplay of host microbiota, genetic perturbations, and inflammation promotes local development of intestinal neoplasms in mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 1 Downloadable Sample
- Illumina MouseRef-8 v2.0 expression beadchip
Description
The preferential localization of some neoplasms, such as serrated polyps, in specific areas of the intestine suggests that non-genetic factors may be important for their development. To test this hypothesis, we took advantage of transgenic mice that expressed HB-EGF throughout the intestine, but develop serrated polyps only in the cecum.
Publication Title
Interplay of host microbiota, genetic perturbations, and inflammation promotes local development of intestinal neoplasms in mice.
Sample Metadata Fields
Specimen part
View Samples