RNA-seq of PBMCs to investigate peptide vaccine immunotherapy biomarkers and response patterns in pediatric gliomas
Ontology highlight
ABSTRACT:
INSTRUMENT(S): NextSeq 500
ORGANISM(S): Homo sapiens
SUBMITTER: Gary Kohanbash
PROVIDER: E-MTAB-6270 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Background<br>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. <br>Methodology/Principal findings<br>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 patients 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. <br>Conclusions/Significance<br>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.<br>
2011-09-07 | E-MEXP-2909 | biostudies-arrayexpress
Project description:Background<br>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. <br>Methodology/Principal findings<br>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. <br>Conclusions/Significance<br>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.<br>
2011-09-07 | E-MEXP-2910 | biostudies-arrayexpress
Project description:Glioma study (gene expression and CGH): Brain tumours are the most common solid tumors in children and have the highest mortality rate of all solid pediatric tumours. Despite advances in multimodality therapy, children with high-grade gliomas invariably have an Overall Survival (OS) around 20% at 5 years. There is growing evidence that the biological knowledge and the histo-prognostic classifications used for the management of adult HGG may not fully apply to children. Interobserver variability and specificity of pediatric tumors with respect to the World Health Organization (WHO) classification have lead to a high rate of misclassification in multi-institutional studies. From 90 biopsies of children with HGG (High Grade Glioma), comprising 37 DIPG (Diffuse Infiltrating Pontine Glioma), 73 extracted RNA have been hybrized on Agilent 4x44K GE arrays and 71 extracted DNA have been hybrized on Agilent 44K and 4x44K CGH arrays. The dataset contains raw data files from Feature Extraction. Genomic data were jointly analysed with clinical and histological data comprising: date_of_diagnosis, date_of_last_news, WHO_grade, deceased_at_median_survival_time, deceased_at_2years, localization of the tumour in brain, gadolinium_T1_inf_T2. A specific analysis was performed on DIPG.
2012-02-22 | E-TABM-1107 | biostudies-arrayexpress
Project description:We have used Illumina Infinium HumanMethylation450 BeadChip array profiling to profile paediatric high grade gliomas within the HERBY clinical trial. The HERBY trial was a phase-II open-label, randomised, multicentre trial evaluating bevacizumab in patients with newly-diagnosed non-brainstem HGG between the ages of 3-18yrs. The 450K methylation array was used to separate brain tumour samples on the basis of their methylation profiles which represent the cell of origin the time and place in which tumours arise. Methylation arrays provide data for an integrated molecular diagnosis of brain tumours and define specific molecular subgroups and subtypes of high grade gliomas carrying distinct driver mutations and patterns of somatic alterations.
2018-05-11 | E-MTAB-5552 | biostudies-arrayexpress
Project description:We have used Illumina Infinium HumanMethylation450 BeadChip array profiling to profile paediatric high grade gliomas and diffuse intrinsic pontine gliomas. The 450K methylation array is being used to separate brain tumour samples on the basis of their methylation profiles which represent the cell of origin the time and place in which tumours arise. Methylation arrays provide data for an integrated molecular diagnosis of brain tumours and define specific molecular subgroups and subtypes of high grade gliomas carrying distinct driver mutations and patterns of somatic alterations. These data form part of an integrated meta-analysis of high grade gliomas in children combining DNA copy number, methylation and high throughput sequencing datasets.
2017-09-28 | E-MTAB-5528 | biostudies-arrayexpress
Project description:With the increasing use of immunotherapy in cancer, understanding the tumor immune microenvironment (TIME) has become increasingly important. There has been great success in treatment of some pediatric high-grade gliomas with immune checkpoint inhibition, however overall, the immune microenvironment in pediatric brain tumors remains poorly understood. Accordingly, we developed a clinical immune-oncology gene expression assay and used it to profile a diverse range of pediatric brain tumors with detailed clinical and molecular annotation, including a total of 1379 cases. Our findings demonstrate the critical importance of understanding the TIME to guide the prognosis and management of pediatric brain tumors. In pediatric low-grade gliomas we identified distinct patterns of immune activation with prognostic significance in BRAF V600E mutant tumors. In pediatric high-grade gliomas, we observed elevated inflammation and T cell infiltrates in tumors that have historically been considered immune cold, as well as genomic correlates of inflammation levels. In our cohort of mismatch repair deficient high-grade gliomas treated with immune checkpoint inhibition, we found that high tumor inflammation signature was a significant predictor of treatment response. Furthermore, we demonstrated the potential for multimodal biomarkers to improve the treatment stratification of these patients. Importantly, while overall patterns of immune activation were observed for histologically and genomically defined tumor types, there was nonetheless significant variability within each diagnostic entity, indicating that the immune response must be evaluated as an independent feature. In sum, in addition to the histology and molecular profile, this work establishes the importance of assessing and reporting on the tumor immune microenvironment as an essential axis of cancer diagnosis in the era of personalized medicine.
2024-02-19 | GSE227756 | GEO
Project description:Purpose: More than 90% of children with diffuse intrinsic pontine glioma (DIPG) die within 2 years of diagnosis. There is a dire need to identify therapeutic targets, however lack of patient material for research has limited progress. We evaluated a large cohort of diffuse intrinsic pontine gliomas (DIPGs) to identify recurrent genomic abnormalities and gene expression signatures underlying DIPG. Patients and Methods: We used single nucleotide polymorphism arrays to evaluate genomic copy number imbalances in 43 DIPGs from 40 patients and in 8 low-grade exophytic brainstem gliomas. Gene expression arrays were used to evaluate expression signatures from 27 DIPGs, 6 low-grade exophytic brainstem gliomas and 66 low-grade gliomas arising outside the brainstem. Results: Frequencies of specific large-scale and focal imbalances varied significantly between DIPGs and pediatric glioblastomas outside the brainstem. Focal amplifications of genes within the receptor tyrosine kinase-Ras-PI3-kinase signaling pathway were found in 47% of DIPG, with PDGFRA and MET showing the highest frequency. 30% of DIPG contained focal amplifications of cell-cycle regulatory genes controlling RB phosphorylation, and 21% had concurrent amplification of genes from both pathways. Some tumors showed heterogeneity in amplification patterns. DIPGs showed distinct gene expression signatures relating to developmental processes compared to pediatric glioblastomas arising outside the brainstem, while expression signatures of low-grade exophytic brainstem gliomas were similar to low-grade gliomas outside the brainstem. Copy number analaysis: 43 DIPG samples, 8 Low Grade Gliomas using SNP6.0. Available matched normals are also profiled with SNP6.0. Expression analysis: 29 DIPG samples, 6 Low grade samples Please contact Suzanne Baker at Suzanne.Baker@stjude.org for CEL files and genotype calls.
2011-09-20 | E-GEOD-26576 | biostudies-arrayexpress
Project description:MAPK inhibitor sensitivity scores (MSS) were developed to predict sensitivity to MAPK inhibitors in pediatric low-grade gliomas (pLGG). The scores were validated in pLGG cell lines in vitro and in the publicly available Open Pediatric Brain Tumor Atlas dataset. Validation in independent datasets is warranted.
2023-06-28 | GSE222405 | GEO
Project description:MAPK inhibitor sensitivity scores (MSS) were developed to predict sensitivity to MAPK inhibitors in pediatric low-grade gliomas (pLGG). The scores were validated in pLGG cell lines in vitro and in the publicly available Open Pediatric Brain Tumor Atlas dataset. Validation in independent datasets is warranted.
2023-06-28 | GSE222404 | GEO
Project description:Purpose: More than 90% of children with diffuse intrinsic pontine glioma (DIPG) die within 2 years of diagnosis. There is a dire need to identify therapeutic targets, however lack of patient material for research has limited progress. We evaluated a large cohort of diffuse intrinsic pontine gliomas (DIPGs) to identify recurrent genomic abnormalities and gene expression signatures underlying DIPG. Patients and Methods: We used single nucleotide polymorphism arrays to evaluate genomic copy number imbalances in 43 DIPGs from 40 patients and in 8 low-grade exophytic brainstem gliomas. Gene expression arrays were used to evaluate expression signatures from 27 DIPGs, 6 low-grade exophytic brainstem gliomas and 66 low-grade gliomas arising outside the brainstem. Results: Frequencies of specific large-scale and focal imbalances varied significantly between DIPGs and pediatric glioblastomas outside the brainstem. Focal amplifications of genes within the receptor tyrosine kinase-Ras-PI3-kinase signaling pathway were found in 47% of DIPG, with PDGFRA and MET showing the highest frequency. 30% of DIPG contained focal amplifications of cell-cycle regulatory genes controlling RB phosphorylation, and 21% had concurrent amplification of genes from both pathways. Some tumors showed heterogeneity in amplification patterns. DIPGs showed distinct gene expression signatures relating to developmental processes compared to pediatric glioblastomas arising outside the brainstem, while expression signatures of low-grade exophytic brainstem gliomas were similar to low-grade gliomas outside the brainstem.
2011-09-21 | GSE26576 | GEO