Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression data from human brain tumors and human normal brain

ABSTRACT: The characteristics of immune cells infiltrating pediatric brain tumors is largely unexplored. A better understanding of these characteristics will provide a foundation for development of immunotherapy for pediatric brain tumors. Gene expression profiles were used to identify immune marker gene that are differentially expressed between various brain tumor types. Gene expression profiles were generated from surgical tumor and normal brain samples (n=130) using Affymetrix HG-U133plus2 chips (Platform GPL570). Gene expression profiles of different types of brain tumors and normal brain were filtered to obtain gene expression of key immune cell markers. Comparative analyses between different brain tumors and normal brain was used to identifiy differential immune characteristics of these tumors.

ORGANISM(S): Homo sapiens

SUBMITTER: Andrew Donson

PROVIDER: E-GEOD-50161 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Characterization of distinct immunophenotypes across pediatric brain tumor types.

Griesinger Andrea M AM Birks Diane K DK Donson Andrew M AM Amani Vladimir V Hoffman Lindsey M LM Waziri Allen A Wang Michael M Handler Michael H MH Foreman Nicholas K NK

Journal of immunology (Baltimore, Md. : 1950) 20130927 9

Despite increasing evidence that antitumor immune control exists in the pediatric brain, these findings have yet to be exploited successfully in the clinic. A barrier to development of immunotherapeutic strategies in pediatric brain tumors is that the immunophenotype of these tumors' microenvironment has not been defined. To address this, the current study used multicolor FACS of disaggregated tumor to systematically characterize the frequency and phenotype of infiltrating immune cells in the mo ...[more]

PMID: 24078694

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Project description:Introduction: Pediatric adamantinomatous craniopharyngioma (ACP) is a histologically benign but clinically aggressive brain tumor that arises from the sellar/suprasellar region. Despite a high survival rate with current surgical and radiation therapy (75-95% at 10 years), ACP is associated with debilitating visual, endocrine, neurocognitive and psychological morbidity, resulting in exceptionally poor quality of life for survivors. Identification of an effective pharmacological therapy would drastically decrease morbidity and improve long term outcomes for children with ACP. Results: Using microarray analysis of 15 ACP patient samples, we have found several pharmaceutical targets that are significantly and consistently overexpressed in our panel of ACP relative to other pediatric brain tumors, pituitary tumors, normal pituitary and normal brain tissue. Among the most highly expressed are several targets of the kinase inhibitor dasatinib -- LCK, EPHA2 and SRC; EGFR pathway targets -- AREG, EGFR and ERBB3; and other potentially actionable cancer targets -- SHH, MMP9 and MMP12. We confirm by Western blot that a subset of these targets is highly expressed in ACP primary tumor samples. Discussion: We report here the first microarray gene expression analysis for ACP and the identification of targets for rational therapy. Experimental drugs targeting each of these gene products are currently being tested clinically and pre-clinically for the treatment of other tumor types. This study provides a rationale for further pre-clinical and clinical studies of novel pharmacological treatments for ACP. Development of pre-clinical mouse and cell culture models for ACP will further enable the translation of these targets from the lab to the clinic. Gene expression profiles were generated from surgical tumor and normal brain samples (n=210) using Affymetrix HG-U133 Plus 2.0 chips. Gene expression profiles of adamantinomatous craniopharyngioma (ACP) were compared to a cohort of other tumor samples and normal brain tissues, and analyzed via gene set enrichment (GSEA analysis) and hierarchical clustering analysis to identify high expression of potential drug targets. The sample metadata and processed data for the complete dataset, which includes reanalysis of 23 Samples from GSE26966, 33 Samples from GSE35493, and 42 Samples from GSE50385, are linked below as supplementary files.

Project description:Rhabdoid tumors (RTs) are aggressive tumors of early childhood that occur most often in brain (AT/RTs) or kidney (KRTs). Regardless of location, they are characterized by loss of functional SMARCB1 protein, a component of the SWI/SNF chromatin remodeling complex. The aim of this study was to determine genes and biological process dysregulated in common to both AT/RTs and KRTs. Gene expression for AT/RTs was compared to that of other brain tumors and normal brain using microarray data from our lab. Similar analysis was performed for KRTs and other kidney tumors and normal kidney using data from GEO. Dysregulated genes common to both analyses were analyzed for functional significance. Unsupervised hierarchical clustering of RTs identified 3 major subsets: 2 comprised of AT/RTs, and 1 of KRTs. Compared to other tumors, 1187, 663 and 539 genes were dysregulated in each subset, respectively. Only 14 dysregulated genes were common to all 3 subsets. Compared to normal tissue, 5209, 4275 and 2841 genes were dysregulated in each subset, with an overlap of 610 dysregulated genes. Among these genes, processes associated with cell proliferation, MYC activation, and epigenetic dysregulation were common to all 3 RT subsets. The low overlap of dysregulated genes in AT/RTs and KRTs suggests that factors in addition to SMARCB1 loss play a role in determining subsequent gene expression. Drugs which target cell cycle or epigenetic genes may be useful in all RTs. Additionally, targeted therapies tailored to specific RT subset molecular profiles should be considered. Molecular profiling of 20 ATRTs, 42 other pediatric CNS WHO Grade IV tumor samples and 9 pediatric normal brain samples was performed using Affymetrix U133 Plus2 GeneChips. Data were background corrected and normalized using gcRMA (as implemented in Bioconductor). ANOVA was used to identify differentially expressed genes for AT/RTs compared to other brain tumor types. Various analyses, including bioinformatics tools DAVID, Gene Set Enrichment (GSEA), and Ingenuity Pathways Analysis, were used to identify biological processes and genes of particular interest among the differentially expressed genes. Similar analysis of publicly available KRT and pediatric kidney tumor and normal kidney data was also performed by us. The overlaps between the results were examined to determine genes and processes dysregulated in common to both ATRTs and KRTs. This study includes a re-analysis of samples from other studies (AT/RT: GSE28026; glioblastoma: GSE33331).

Project description:Pediatric embryonal brain tumor (PEBT), which includes medulloblastoma (MB), primitive neuroectodermal tumor (PNET) and atypical teratoid/rhabdoid tumor (AT/RT), is the second most prevalent pediatric tumor type among brain tumors of childhood. AT/RT is highly malignant and is often misdiagnosed as MB and PNET. Distinguishing AT/RT from PNET/MB is of clinical significance since the survival rate of AT/RT patients is much lower. The diagnosis of AT/RT relies primarily on the morphologic assessment and immunohistochemistry (IHC) staining on a few known markers such as the lack of INI1 protein expression. However, in our clinical practice we observed several AT/RT-like tumors, which fulfilled histopathologic and all other biomarker criteria for AT/RT diagnosis, still showed retained INI1 immunoreactivity. Recent studies also reported retained INI1 immunoreactivity among certain diagnosed AT/RTs. It is therefore necessary to re-evaluate INI1(+), AT/RT-like cases. Sanger sequencing, array CGH and mRNA microarray analyses were performed on PEBT samples for studying their genomics landscapes. AT/RT and INI(+) AT/RT-like patients had similar survival rate, and global array CGH analysis and INI1 gene sequencing showed there is no differential chromosomal aberration marker between INI1(-) AT/RT and INI(+) AT/RT-like cases. We did not misdiagnose MB or PNET as AT/RT-like cases since transcriptome profiling revealed that not only AT/RT and INI(+) AT/RT-like cases expressed distinct mRNA and microRNA profiles, and their gene expression patterns were different from those of MBs and PNETs. AT/RTs shared the closest transcriptome profile to embryonic stem cells, INI1(+) AT/RT-like tumors were more similar to somatic neural stem cell, while MBs were closer to fetal brain. Novel biomarkers were identified to distinguish INI1(-) AT/RTs, INI1(+) AT/RT-like cases and MBs. Our studies disclosed a novel INI1(+) ATRT-like subtype among Taiwanese pediatric cases. New diagnostic biomarkers, as well as new therapeutic tactics, can be developed according to the transcriptome information unveiled in this work. 2 AT/RT-like cases and 7 AT/RT cases are subjected to transcriptome analysis.

Project description:Background Primitive brain tumors are the first cause of cancer-related death in children. Tumor cells with stem-like properties (TSCs), thought to account for tumorigenesis and therapeutic resistance, have been isolated from high-grade gliomas in adults. Whether TSCs are a common component of pediatric brain tumors and are of clinical relevance remains to be determined. Methodology/Principal findings Tumor cells with self-renewal properties were isolated with cell biology techniques from a majority of 55 pediatric brain tumors samples, regardless of their histopathologies and grades of malignancy (57% of embryonal tumors, 57% of low-grade gliomas and neuro-glial tumors, 70% of ependymomas, 91% of high-grade gliomas). The vast majority (10/12) of high-grade glioma-derived oncospheres sustained long-term self-renewal numbers akin to neural stem cells (>7 self-renewals), whereas cells with limited renewing abilities akin to neural progenitors dominated in all other tumor types. Regardless of tumor entities, the young age group was associated with self-renewal properties akin to neural stem cells (P=0.05, chi-square test). TSCs shared a complex molecular profile combining embryonic stem cell markers with elements controlling neural stem cell properties and epithelio-mesenchymal transitions. They were radio- and chemoresistant and formed aggressive tumors after intracerebral grafting. Survival analysis of the cohort showed an association between isolation of TSCs with long-term self-renewal abilities and a patientM-^Rs higher mortality rate (P = 0.022, log-rank test). Patients bearing cells with limited self-renewal properties constituted an intermediate group of survival but which did not reach statistical significance. Conclusions/Significance In brain tumors affecting adult patients, TSC have been isolated only from high-grade gliomas. In contrast, our data show that tumor cells with stem cell-like or progenitor-like properties can be isolated from a wide range of histological sub-types and grades of pediatric brain tumors. They suggest that cellular mechanisms fueling tumor development differ between adult and pediatric brain tumors.

Dataset Information

Expression data from human brain tumors and human normal brain

Publications

Characterization of distinct immunophenotypes across pediatric brain tumor types.

Similar Datasets

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