Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Next Generation Sequencing of Diffuse Intrinsic Pontine Glioma Samples

ABSTRACT:

Diffuse intrinsic pontine glioma (DIPG) is an extremely rare (~350 cases/year) and universally fatal childhood brain cancer. Standard clinical strategies such as chemotherapy and radiotherapy show only transient improvement in patient condition and result in negligible change in survival, DIPG remains at below 1% survival after 5 years. Prioritization of panobinostat through previous cooperative work resulted in a phase 1 clinical trial. Nonetheless, new therapies for DIPG must be identified to further dramatically change the statistics for DIPG.

To identify novel therapy strategies for DIPG, we performed whole exome(16 new samples, 22 previously published samples, 38 in total with 26 matched normal) and RNA deep sequencing (17 new samples, 11 previously published samples) on a cohort of new patient samples. Sequencing results aid in the identification of recurrent mutations/variations and endotypic expression profiling to identify new therapeutic and treatment strategies for DIPG.

PROVIDER: phs001526 | dbGaP |

REPOSITORIES: dbGaP

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	GapExchange_phs001526.v1.p1.xml	Xml
	dbGaPEx2.1.5.xsd	Other
	Study_Report.phs001526.DIPG.v1.p1.MULTI.pdf	Pdf
	manifest_phs001526.DIPG.v1.p1.c1.GRU.pdf	Pdf
	manifest_phs001526.DIPG.v1.p1.c2.GRU-COL.pdf	Pdf

Items per page:

1 - 5 of 17

Similar Datasets

Low Expression of SP1 has a Different Effect on Intestinal-type compared to Diffuse-type Gastric Adenocarcinoma

Project description:Specificity protein 1 (SP1) is an essential transcription factor regulating multiple cancer-related genes. Since aberrant expression of SP1 was known to be related to cancer development and progression, we focused on SP1 expression in gastric carcinoma and its correlation with disease outcomes. We discovered a different relationship between SP1 expression and patient survival in intestinal- and diffuse-type gastric cancer. In diffuse-type gastric cancer, patient survival decreased as SP1 expression increased (P < 0.05) in accordance with previously published papers, whereas the lack of SP1 expression in intestinal-type gastric cancer was correlated significantly with poor survival (P < 0.05). When SP1 downregulation was forced in high SP1 expressor intestinal-type gastric cell line MKN28 with siRNA, both migration and invasion were increased but cell proliferation was decreased. In accordance with these results, microarray data in siRNA-transfected MKN28 showed that genes inhibiting migration were downregulated and the expression of genes negatively facilitating proliferation was increased. Both migration and invasion, however, in low SP1 expressor intestinal-type gastric cell line AGS were decreased by forced SP1 expression. In contrast to intestinal-type, in diffuse-type gastric cell line SNU484, high SP1 expressor, both migration and invasion were decreased by siRNA. Contrary to previous studies, which did not reflect differences between the 2 histological types, our results showed that low expression of SP1 is involved in cancer progression and metastasis, and has a different effect on intestinal-type compared to diffuse-type gastric adenocarcinoma. 2 samples for MKN28 cells: si-SP1 against si-control and dyeswap of it upon 72 hour

2012-01-01 | E-GEOD-34792 | biostudies-arrayexpress

Prediction of survival in diffuse large B cell lymphoma treated with chemotherapy plus Rituximab

Project description:Gene expression profiling of DLBCL patient samples was performed to investigate, whether molecular gene expression signatures retain their prognostic significance in patients treated with chemotherapy plus Rituximab. The lymphnode, germinal center signature and a new angiogenesis signature were combined to a final multivariate model which defined quartile groups among Rituximab-CHOP-treated patients with distinct 3-year overall survival rates. Keywords: clinical history design

2008-11-28 | GSE10846 | GEO

Low Expression of SP1 has a Different Effect on Intestinal-type compared to Diffuse-type Gastric Adenocarcinoma

2012-01-01 | GSE34792 | GEO

Genes reflect the common recent history of the Uralic-speaking populations

Project description:We genotyped 135 new samples (121 samples from 10 Uralic-speaking and 14 samples from 8 non-Uralic-speaking populations) and combined these data with previously published data to characterize the population structure of Uralic-speaking populations in the context of their geographic neighbours across Eurasia

2018-08-13 | GSE108646 | GEO

The Genetic Legacy of the Expansion of Turkic-Speaking Nomads Across Eurasia

Project description:We genotyped 322 new samples from 38 Eurasian populations and combined it with previously published data to characterize the population structure of Turkic-speaking populations in the context of their geographic neighbors across Eurasia

2015-02-21 | GSE66157 | GEO

Genome-wide mapping of histone H3 lysine 27 acetylation in acute myeloid leukemia

Project description:Somatic mutations are rare in pediatric AML (pAML), indicating alternate strategies are needed to identify new, pediatric AML-specific, druggable targets. We defined the enhancer landscape of 22 pAML patient samples and observed many known leukemia regulators are SE-associated in pAML. The retinoic acid receptor alpha (RARA) gene was differentially regulated in our cohort and present in all cyto/molecular subtypes tested, totaling 64% of the pAML samples. RARA SE-positive pAML cell lines and samples had higher RARA mRNA levels than RARA SE-negative samples and also were specifically sensitive to the synthetic RARA agonist tamibarotene in vitro, with halted proliferation and upregulated retinoid target genes. Tamibarotene prolonged survival and suppressed the leukemia burden of a RARA SE-positive pAML patient-derived xenograft (PDX) mouse model compared to a RARA SE-negative PDX. These data demonstrate the utility of leveraging chromatin regulation to identify new dependencies in pediatric AML and specifically lay the preclinical foundation for a tamibarotene trial in children with relapsed/refractory AML.

2021-08-01 | GSE155558 | GEO

The genetic ancestry of modern Indus Valley populations from Northwest India

Project description:We genotyped 45 new samples from 4 populations of Northwest India and combined it with previously published data to characterize the population structure of modern Northwest Indian populations in the context of their geographic neighbors across South Asia and West Eurasia.

2018-12-05 | GSE119653 | GEO

Non-inflammatory tumor microenvironment of Diffuse Intrinsic Pontine Glioma (DIPG)

Project description:Diffuse intrinsic pontine glioma (DIPG) is a universally fatal malignancy of the childhood central nervous system, with a median overall survival of 9-11 months. We have previously shown that primary DIPG tissue contains numerous tumor-associated macrophages, and substantial work has demonstrated a significant pathological role for adult glioma-associated macrophages. However, work over the past decade has highlighted many molecular and genomic differences between pediatric and adult glioblastomas (GBM). Thus, we directly compared inflammatory characteristics of DIPG and adult GBM. We found that the leukocyte (CD45+) compartment in primary DIPG tissue samples is predominantly composed of CD11b+ macrophages, with very few CD3+ T-lymphocytes. In contrast, T-lymphocytes are more abundant in adult GBM tissue samples. RNA sequencing of macrophages isolated from primary tumor samples revealed that DIPG- and adult GBM-associated macrophages both express gene programs related to ECM remodeling and angiogenesis, but DIPG-associated macrophages express substantially fewer inflammatory factors than their adult GBM counterparts. Examining the secretome of glioma cells, we found that patient-derived DIPG cell cultures secrete markedly fewer cytokines and chemokines than patient-derived adult GBM cultures. Concordantly, bulk and single-cell RNA sequencing data indicates low to absent expression of chemokines and cytokines in DIPG. Together, these observations suggest that the inflammatory milieu of the DIPG tumor microenvironment is fundamentally different than adult GBM. The low intrinsic inflammatory signature of DIPG cells may contribute to the lack of lymphocytes and non-inflammatory phenotype of DIPG-associated microglia/macrophages. Understanding the glioma subtype-specific inflammatory milieu may inform the design and application of immunotherapy-based treatments.

2018-08-23 | GSE115397 | GEO

PTEN loss deM-oM-,M-^Anes a PI3K/AKT pathway-dependent germinal center subtype of diffuse large B-cell lymphoma

Project description:Diffuse large B-cell lymphoma (DLBCL) represents a heterogeneous diagnostic category with distinct molecular subtypes that can be deM-oM-,M-^Aned by gene expression proM-oM-,M-^Aling. However, even within these deM-oM-,M-^Aned subtypes, heterogeneity prevails. To further elucidate the pathogenesis of these entities, we determined the expression of the tumor suppressor phosphatase and tensin homolog (PTEN) in 248 primary DLBCL patient samples. These analyses revealed that loss of PTEN was detectable in 55% of germinal center B-cell-like (GCB) DLBCLs, whereas this abnormality was found in only 14% of non-GCB DLBCL patient samples. In GCB DLBCL, the PTEN status was inversely correlated with activation of the oncogenic PI3K/ protein kinase B (AKT) pathway in both DLBCL cell lines and primary patient samples. Reexpression of PTEN induced cytotox- icity in PTEN-deM-oM-,M-^Acient GCB DLBCL cell line models by inhibiting PI3K/AKT signaling, indicating an addiction to this pathway in this subset of GCB DLBCLs. PI3K/AKT inhibition induced down-regulation of the transcription factor MYC. Reexpression of MYC rescued GCB DLBCL cells from PTEN-induced toxicity, identifying a regulatory mechanism of MYC expression in DLBCL. Finally, pharmacologic PI3K inhibition resulted in toxicity selectively in PTEN-deM-oM-,M-^Acient GCB DLBCL lines. Collectively, our results indicate that PTEN loss deM-oM-,M-^Anes a PI3K/ AKT-dependent GCB DLBCL subtype that is addicted to PI3K and MYC signaling and suggest that pharmacologic inhibition of PI3K might represent a promising therapeutic approach in these lymphomas. This GEO dataset is comprised of a) GEP measurements for 34 primary DLBCL patient samples plus two reference samples, b) 8 paired GEP measurements of the HT DLBCL cell line and c) aCGH measurements for two DLBCL cell lines in addition to previously published cell lines in GSE43272 (i.e., Sample GSM1059798). All of these data were used in the paper cited below.

2013-07-09 | E-GEOD-45495 | biostudies-arrayexpress

Molecular changes during progression from early stage to advanced urothelial carcinoma

Project description:It is unclear how urothelial carcinoma of the urinary bladder change, genetically and phenotypically, as patients progress from recurrent non muscle-invasive (NMI) to muscle-invasive (MI) disease or disease that require radical cystectomy. This data set contains gene expression data from 200 samples in a longitudinal study of such patients. Overlap with previously GEO-published cohorts from our lab is described in the metadata.

2020-01-20 | GSE128959 | GEO