Relapsed Medulloblastoma Methylation array
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Stacey Richardson
PROVIDER: E-MTAB-9432 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Study of DNA methylation array data for paired diagnostic and relapse medulloblastoma tumour samples
2023-09-01 | E-MTAB-9430 | biostudies-arrayexpress
Project description:We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC gene family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this molecular group died of rapidly progressive disease post-relapse. To study this genetic interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of Trp53 function in this model produced aggressive tumors that mimicked the characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity, genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53–MYC interactions which emerge at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically. Using this dataset, assignation of medulloblastoma molecular subgroup by Illumina 450k microarray was performed for diagnostic and relapsed medulloblastoma samples to compare subgroup membership at diagnosis and relapse. We investigated the DNA methylation profiles of 18 diagnostic and 22 relapsing samples (including 15 diagnostic / relapse pairs) using the Illumina 450k methylation microarray
2015-04-23 | E-GEOD-62618 | biostudies-arrayexpress
Project description:We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC gene family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this molecular group died of rapidly progressive disease post-relapse. To study this genetic interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of Trp53 function in this model produced aggressive tumors that mimicked the characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity, genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53–MYC interactions which emerge at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically. Using this dataset, assignation of medulloblastoma molecular subgroup by Illumina 450k microarray was performed for diagnostic and relapsed medulloblastoma samples to compare subgroup membership at diagnosis and relapse.
2015-04-23 | GSE62618 | GEO
Project description:Despite improvement of current treatment strategies and novel targeted drugs, relapse and treatment resistance determine the major cause of death for acute myeloid leukemia (AML) patients. To identify the underlying molecular characteristics, numerous studies have been aimed to decipher the genomic- and transcriptomic landscape of AML. Nevertheless, further molecular changes allowing malignant cells to escape treatment are yet to be elucidated. Mass spectrometry is a powerful tool enabling detailed insights into proteomic changes that could explain AML relapse and resistance. Here, we investigated AML samples from 47 adult and 22 pediatric patients at serial time-points during disease progression using high resolution isoelectric focusing liquid chromatography mass spectrometry. We show that the proteomic profile at relapse is enriched for mitochondrial ribosomal proteins and subunits of the respiratory chain complex, indicative of reprogrammed energy metabolism from diagnosis to relapse. Further, higher levels of granzymes and lower levels of the anti-inflammatory protein CR1/CD35 suggest an inflammatory signature promoting disease progression. Finally, through a proteogenomic approach, we detected novel peptides, which present a promising repertoire in the search for biomarkers and tumor-specific druggable targets. Altogether, this study highlights the importance of proteomic studies in holistic approaches to improve treatment and survival of AML patients.
2023-01-09 | PXD031107 | Pride
Project description:Medulloblastoma, the most common malignant pediatric brain tumour, disseminates by shedding cells into the cerebrospinal fluid, which then re-implant to cover the surface of the brain and spinal cord. Metastases are a very poor prognostic sign at presentation and are usually lethal at recurrence. Mechanisms driving dissemination have been described in the bulk primary tumour, with the underlying assumption that primary tumour and metastases are biologically similar. Here we show that in both mouse and human medulloblastoma, multiple metastases from a single animal are extremely similar, but are genetically highly divergent from the primary tumour. Clonal genetic events in the metastases can be demonstrated in a restricted sub-clone of the primary tumour, suggesting that only rare cells within the primary tumour have the ability to metastasize. Failure to account for the bicompartmental nature of primary and metastatic medulloblastoma represents a major barrier to the development of effective targeted therapies. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved human medulloblastoma tissue samples. Copy number analysis of Affymetrix SNP6 arrays was performed for 17 pediatric medulloblastoma samples. Samples comprise a series of 7 patient-matched primary/metastatic cases.
2011-12-09 | E-GEOD-34280 | biostudies-arrayexpress
Project description:The childhood brain tumour medulloblastoma includes four subtypes with very different prognoses. Here, we show that paracrine signals driven by mutant Beta-Catenin in WNT-medulloblastoma â an essentially curable form of the disease â induce an aberrant fenestrated vasculature that permits the accumulation of high levels of intra-tumoural chemotherapy and a robust therapeutic response. In contrast, SHH-medulloblastoma â a less curable disease subtype â contains an intact blood brain barrier, rendering this tumour impermeable and resistant to chemotherapy. Remarkably, the medulloblastoma-endothelial cell paracrine axis can be manipulated in vivo, altering chemotherapy permeability and clinical response. Thus, medulloblastoma genotype dictates tumour vessel phenotype, explaining in part the disparate prognoses among medulloblastoma subtypes and suggesting an approach to enhance the chemoresponsiveness of other brain tumours. We used microarrays to detail the global program of gene expression within endothelial cells from normal mouse hindbrain and genetic mouse models of different medulloblastoma subtypes to identify and verify up-regulated and down-regulated genes Endothelial cells were isolated from adult mouse hindbrain and genetic mouse models of Wnt and Shh-medulloblastoma using Cd-144 and Cd-105 antibodies based magnetic sorting. RNA was extracted and used for hybridization on Affymetrix microarrays. We sought to identify changes in endothelial gene expression patterns based on the surrounding microenvironment, so we purified endothelial cells from normal mouse brain or tumors from genetic mouse models. These include the Shh-medulloblastoma model (Ptch+/-; Ink4c -/-) and Wnt-medulloblastoma model (Blbp-Cre; mutant Ctnnb1+/-; p53-/-; mutant Pik3ca +/-)
2016-04-05 | E-GEOD-73753 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE28460: Expression data from ALL diagnosis and relapse pediatric acute lymphoblastic leukemia cases GSE28461: Promoter methylation data from ALL diagnosis and relapse pediatric acute lymphoblastic leukemia cases Refer to individual Series
2011-09-22 | E-GEOD-28462 | biostudies-arrayexpress
Project description:Multiple myeloma (MM) is a common hematological malignancy with poorly understood recurrence and relapse mechanisms. Notably, bortezomib resistance leading to relapse makes MM treatment significantly challenging. To clarify the drug resistance mechanism, we employed a quantitative proteomics approach to identify differentially expressed protein candidates implicated in bortezomib-resistant recurrent and relapsed MM (RRMM). Bone marrow biopsy specimens from five patients newly diagnosed with MM (NDMM) were compared with those from five patients diagnosed with bortezomib-resistant RRMM using tandem mass tag-mass spectrometry (TMT-MS). Subcellular localization and functional classification of the differentially expressed proteins were determined by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and hierarchical clustering. Top candidates identified were validated with parallel reaction monitoring (PRM) analysis using tissue samples from 11 NDMM and 8 RRMM patients, followed by comparison with the NCBI Gene Expression Omnibus (GEO) dataset of 10 MM patients and 10 healthy controls (Accession No.: GSE80608). Thirty-four differentially expressed proteins in RRMM, including proteinase inhibitor 9 (SERPINB9) were identified by TMT-MS. Subsequent functional enrichment analyses of the identified protein candidates indicated their involvement in regulating cellular metabolism, apoptosis, programmed cell death, lymphocyte-mediated immunity, and defense response pathways in RRMM. The top protein candidate SERPINB9 was confirmed by PRM analysis as well as by comparison with an NCBI GEO dataset. We elucidated the proteome landscape of bortezomib-resistant RRMM and identified SERPINB9 as a promising novel therapeutic target. Our results provide a resource for future studies on the mechanism of RRMM.
2021-03-03 | PXD022182 | Pride
Project description:Molecular classification of medulloblastoma is critical for the correct treatment of this malignant paediatric brain tumour. The analysis of genome-wide DNA methylation patterns has profoundly improved diagnostic precision and classification of brain tumours. However, the implementation of DNA methylation microarrays in daily clinical practice can be time-consuming, costly and inaccessible for many centres worldwide. We aimed to develop a machine-learning decision support system for rapid and cost-effective prediction of medulloblastoma methylation class directly from quantitative PCR data.
2023-08-23 | GSE210723 | GEO
Project description:The childhood brain tumour medulloblastoma includes four subtypes with very different prognoses. Here, we show that paracrine signals driven by mutant Beta-Catenin in WNT-medulloblastoma – an essentially curable form of the disease – induce an aberrant fenestrated vasculature that permits the accumulation of high levels of intra-tumoural chemotherapy and a robust therapeutic response. In contrast, SHH-medulloblastoma – a less curable disease subtype – contains an intact blood brain barrier, rendering this tumour impermeable and resistant to chemotherapy. Remarkably, the medulloblastoma-endothelial cell paracrine axis can be manipulated in vivo, altering chemotherapy permeability and clinical response. Thus, medulloblastoma genotype dictates tumour vessel phenotype, explaining in part the disparate prognoses among medulloblastoma subtypes and suggesting an approach to enhance the chemoresponsiveness of other brain tumours. We used microarrays to detail the global program of gene expression within endothelial cells from normal mouse hindbrain and genetic mouse models of different medulloblastoma subtypes to identify and verify up-regulated and down-regulated genes
2016-04-05 | GSE73753 | GEO