9a129630-21da-4a0c-bbd0-75c2578cd5e4 - samples
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ABSTRACT:
PROVIDER: EGAD00001007807 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Paired-end WGS data of 10 neuroblastoma patient samples (5 obtained at diagnosis and 5 matched blood samples as controls) used for analysis of telomeric content and sequence composition. Mean coverage is 11-65x per sample. The remaining patient samples of the dataset can be found under accession numbers EGAS00001001308 and EGAS00001005424 and mappings of the patients IDs in the supplementary material of the publication.
| EGAD00001009289 | EGA
Project description:This dataset contains gene expression data from the NRC series (Neuroblastoma Research Consortium) for a total of 283 primary neuroblastoma tumors. All tumor samples are fully annotated including patient age at diagnosis, overall and progresison free survival and MYCN amplification status, enabling subgroup analysis, survival analysis and gene expression network analysis.
2018-07-02 | GSE85047 | GEO
Project description:Background: Since the high relapse rate is considered to be responsible for the poor survival of stage M neuroblastoma patients, we tested whether the genomic information of bone marrow-derived disseminated tumor cells (DTCs) would help to better understand tumor evolution and to characterize the relapse-seeding clone. Methods: Seven samples from different regions of a primary tumor of a stage M neuroblastoma patient, corresponding DTCs at diagnosis, and DTCs and a metastatic tumor at relapse were analyzed by a high-density SNP array. Relapse-associated chromosomal aberrations found in this case were then validated in DTCs and tumor samples of 154 stage M neuroblastoma patients. Findings: In this case study, unique aberrations were evident in certain tissue/time points aside from a high concordance of genomic aberrations between all analyzed samples. Surprisingly, DTCs at diagnosis, and DTCs and the metastatic tumor at relapse all displayed a terminal deletion in 1q which was not detected in any of the primary tumor samples. In the validation cohort, 1q terminal deletions were found with a higher frequency in DTCs at diagnosis (17.8%) and at relapse (27.5%) compared to primary tumors (11%). 1q deletions were significantly associated with 19q and ATRX deletions. The presence of each individual aberration in the diagnostic DTCs was associated with an increased likelihood of an adverse event and in case of 19q deletion with a decreased overall survival. Moreover, PTPRD deletion and loss of chromosome Y had significantly higher frequencies in the relapse samples compared to the diagnostic samples. Interpretation: These data strongly suggest a branched clonal evolution and a parallel progression of primary and metastatic tumor cells. In addition, the higher frequency of relapse-associated genomic aberrations in the diagnostic DTCs compared to the primary tumors and their effect on the event-free survival rate indicate that analysis of DTCs at diagnosis may provide a higher probability for detecting the relapse-seeding clone compared to the primary tumor. Background: Since the high relapse rate is considered to be responsible for the poor survival of stage M neuroblastoma patients, we tested whether the genomic information of bone marrow-derived disseminated tumor cells (DTCs) would help to better understand tumor evolution and to characterize the relapse-seeding clone. Methods: Seven samples from different regions of a primary tumor of a stage M neuroblastoma patient, corresponding DTCs at diagnosis, and DTCs and a metastatic tumor at relapse were analyzed by a high-density SNP array. Relapse-associated chromosomal aberrations found in this case were then validated in DTCs and tumor samples of 154 stage M neuroblastoma patients. Findings: In this case study, unique aberrations were evident in certain tissue/time points aside from a high concordance of genomic aberrations between all analyzed samples. Surprisingly, DTCs at diagnosis, and DTCs and the metastatic tumor at relapse all displayed a terminal deletion in 1q which was not detected in any of the primary tumor samples. In the validation cohort, 1q terminal deletions were found with a higher frequency in DTCs at diagnosis (17.8%) and at relapse (27.5%) compared to primary tumors (11%). 1q deletions were significantly associated with 19q and ATRX deletions. The presence of each individual aberration in the diagnostic DTCs was associated with an increased likelihood of an adverse event and in case of 19q deletion with a decreased overall survival. Moreover, PTPRD deletion and loss of chromosome Y had significantly higher frequencies in the relapse samples compared to the diagnostic samples. Interpretation: These data strongly suggest a branched clonal evolution and a parallel progression of primary and metastatic tumor cells. In addition, the higher frequency of relapse-associated genomic aberrations in the diagnostic DTCs compared to the primary tumors and their effect on the event-free survival rate indicate that analysis of DTCs at diagnosis may provide a higher probability for detecting the relapse-seeding clone compared to the primary tumor.
2017-08-31 | GSE84291 | GEO
Project description:MYCN amplification in neuroblastoma leads to aberrant expression of MYCN oncoprotein, which binds active genes promoting transcriptional amplification. Yet how MYCN coordinates transcription elongation to meet productive transcriptional amplification and which elongation machinery represents MYCN-driven vulnerability remain to be identified. We conducted a targeted screen of transcription elongation factors and identified the super elongation complex (SEC) as a unique vulnerability in MYCN-amplified neuroblastomas. MYCN directly binds EAF1 and recruits SEC to enhance processive transcription elongation. Depletion of EAF1 or AFF1/AFF4, another core subunit of SEC, leads to a global reduction in transcription elongation and elicits selective apoptosis of MYCN-amplified neuroblastoma cells. A combination screen reveals SEC inhibition synergistically potentiates the therapeutic efficacies of FDA-approved BCL2 antagonist ABT-199, in part due to suppression of MCL1 expression, both in MYCN-amplified neuroblastoma cells and in patient-derived xenografts. These findings identify disruption of the MYCN-SEC regulatory axis as a promising therapeutic strategy in neuroblastoma.
2023-05-10 | PXD039332 | Pride
Project description:<p>Relapse and treatment resistance are common in children with high-risk neuroblastoma, and novel therapies are needed. Conventional drug discovery is slow, expensive, often fails in practice, and consequently falls short in addressing pediatric and rare conditions. In such instances, drug repurposing is a promising strategy. Here, we used two independent in silico prediction tools including machine learning to identify approved drugs for repurposing against neuroblastoma. The combination of statins and phenothiazines showed strong synergistic effects in human neuroblastoma organoids, decreased tumor growth and prolonged survival in MYCN-amplified neuroblastoma patient-derived xenografts. The drug combination altered cholesterol metabolism through two different mechanisms and induced a phenotypic change towards an adrenergic state in vitro, which was associated with enhanced chemosensitivity. Integration of the drug combination into standard-of-care chemotherapy regressed tumors and prolonged survival in chemoresistant patient-derived xenografts. Thus, a combination of safe and approved medications added to standard-of-care chemotherapy outperforms chemotherapy alone in chemoresistant neuroblastoma.</p>
2025-11-13 | MTBLS13246 | MetaboLights
Project description:Extrachromosomal DNA (ecDNA) amplification enhances intercellular oncogene dosage variability and accelerates tumor evolution by violating foundational principles of genetic inheritance through its asymmetric mitotic segregation. Spotlighting high-risk neuroblastoma we demonstrate how ecDNA amplification undermines the clinical efficacy of current therapies in cancers with extrachromosomal MYCN amplification. Integrating theoretical models of oncogene copy number-dependent fitness with single-cell ecDNA quantification and phenotype analyses, we reveal that ecDNA copy number heterogeneity drives phenotypic diversity and determines treatment sensitivity through mechanisms unattainable by chromosomal oncogene amplification. We demonstrate that ecDNA copy number directly influences critical cell fate decisions in cancer cell lines, patient-derived xenografts and primary neuroblastomas, illustrating how extrachromosomal oncogene dosage-driven phenotypic diversity offers a strong evolutionary advantage under therapeutic pressure. Furthermore, we identify senescent ecDNA-containing cells with reduced copy numbers in neuroblastomas and other MYC-amplified cancers as a source of treatment resistance and outline a strategy for their targeted elimination to improve the poor outcome of patients with MYCN-amplified cancers.
2025-07-05 | PXD064049 | Pride
Project description:This study corresponds to a re-analysis and meta-analysis of the five transcriptomic studies related to spontaneous tolerance to renal allograft in human. It examines the transcriptome of peripheral blood samples from six distinct clinical groups: healthy volunteers (HV); tolerant patients (TOL); stable patients on minimal immunosuppression (MIS) or maintained on classical immunosuppressive therapy (STA); patients showing either signs of chronic rejection (CR) or acute rejection (AR). The initial studies are the following: -Study 1 from Braud C. et al. (J Cell Biochem., 2008) published under GEO accession number GSE47755 and comprising 250 unique samples (8 HV; 21 TOL; 190 STA; 31 CR). -Study 2 from Brouard S. et al. (Proc Natl Acad Sci U S A., 2007) published under GEO accession number GSE47683 and comprising 67 unique samples (8 HV; 12 TOL; 10 MIS; 12 STA; 11 CR; 14 AR). - Study 3 from Lozano JJ. et al. (Am J Transplant., 2011) published under GEO accession number GSE22707 and comprising 42 unique samples (6 HV; 12 TOL; 12 STA; 12 CR). - Study 4 from Newell KA. et al. (J Clin Invest., 2010) published under GEO accession number GSE22229 and comprising 58 unique samples (12 HV; 19 TOL; 27 STA). - Study 5 from Sagoo P. et al. (J Clin Invest. 2010) published under GEO accession number GSE14655 and comprising two distinct cohorts of patients. The IOT (“Indices of Tolerance”) cohort (5a) corresponds to a European group of patients and totalizes 74 unique samples (8 HV; 10 TOL; 11 MIS; 36 STA; 9 CR). The ITN (“Immune Tolerance in Transplantation”) cohort (5b) corresponds to an American group of patients and totalizes 105 unique samples (20 HV; 22 TOL; 11 MIS; 34 STA; 18 CR). The final data matrix corresponds to the combination of the data from the five independent studies and examines the expression of 1846 meta-genes (MG) across 596 unique blood samples. The 1846 meta-genes correspond to the genes being measured across the five datasets and form a virtual microarray platform (TOL-HUMAN-G1846). The 596 examined samples can be divided into 62 HV, 96 TOL, 32 MIS, 311 STA, 81 CR, and 14 AR.
2015-10-06 | GSE49198 | GEO
Project description:Despite significant progress in the molecular understanding of medulloblastoma, stratification of risk in patients remains a challenge. Focus has shifted from clinical parameters to molecular markers, such as expression of specific genes and selected genomic abnormalities, to improve accuracy of treatment outcome prediction. Here, we show how integration of high-level clinical and genomic features or risk factors, including disease subtype, can yield more comprehensive, accurate, and biologically interpretable prediction models for relapse versus no-relapse classification. We also introduce a novel Bayesian nomogram indicating the amount of evidence that each feature contributes on a patient-by-patient basis. The training set consisted of 96 samples for which relapse status at 30 months post-treatment was known. Matched normal blood samples were collected through the COG Tumor Bank (protocol ACNS02B3) and from Children's Hospital Boston under institutional review board approval. The test set included 78 samples: 47 samples from our original study6 not used for training, 16 samples from Kool et al,33 and 15 samples from the COG Tumor Bank. All training and test samples correspond to patients at least 3 years old treated with conventional chemotherapy, surgical resection, and craniospinal irradiation. In the test set, 15 samples (Children's Oncology Group Tumor Bank) were processed as described above. Of those 15, a total of six have DNA copy number data. Another set of 47 samples was taken from the data set from Pomeroy et al. (Affymetrix Hu6800; Affymetrix). None of those samples had DNA copy number data. The remaining 16 samples, all with DNA copy number data, came from Kool et al. (Affymetrix U133; Affymetrix).
2022-04-28 | GSE201583 | GEO
Project description:ATRX is one of the most frequently mutated genes in high-risk neuroblastoma. ATRX mutations are mutually exclusive with MYCN amplification and mark a recognizable patient subgroup, presenting in older children with chemotherapy-resistant, slowly progressive disease. The mechanisms underlying how ATRX mutations drive high-risk and difficult-to-treat neuroblastoma are still largely elusive. To unravel the role of ATRX in neuroblastoma, we generated isogenic neuroblastoma cell line models of both ATRX loss of-function and ATRX in-frame multi-exon deletions, representing different types of alterations found in patients. RNA-sequencing analysis consistently showed significant upregulation of pathways implicated in inflammatory responses and epithelial-to- mesenchymal transition in the ATRX-mutant cell lines. In vivo, ATRX mutations mediate macrophage recruitment in xenograft models. This was further confirmed in patient-derived xenograft models. In support of this, bioinformatic analysis of previously published neuroblastoma patient data sets revealed an immunogenic phenotype and higher score of macrophages (with no distinction between M1 and M2 macrophage populations) and dendritic cells, but not lymphocytes, in ATRX-mutant versus ATRX wildtype tumors. Histopathological assessment of diagnostic samples from patients with ATRX mutant disease confirmed these findings with more macrophage infiltration compared to MYCN-amplified tumors. In conclusion, these results highlight that in contrast to MYCN-amplified neuroblastoma, which is associated with a cold immune microenvironment, ATRX-mutated neuroblastoma is characterized by a distinct immunogenic phenotype.
2025-02-10 | GSE277158 | GEO
Project description:Despite the identification of MYCN amplification as an adverse prognostic marker in neuroblastoma, MYCN inhibitors have yet to be developed. Here, by integrating evidence from a whole genome shRNA library screen and the computational inference of master regulator proteins, we identify Transcription Factor Activating Protein 4 (TFAP4) as a critical effector of MYCN amplification in neuroblastoma, providing a novel synthetic lethal target. We demonstrate that TFAP4 is a direct target of MYCN in neuroblastoma cells, and that its expression and activity strongly negatively correlate with neuroblastoma patient survival. Silencing TFAP4 selectively inhibits MYCN-amplified neuroblastoma cell growth both in vitro and in vivo, in xenograft mouse models. Mechanistically, silencing TFAP4 induces neuroblastoma differentiation, as evidenced by increased neurite outgrowth and up-regulation of neuronal markers. Taken together, our results demonstrate that TFAP4 is a master regulator of MYCN-amplified neuroblastoma and may represent a valuable novel therapeutic target.
2017-11-15 | GSE102652 | GEO