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High-resolution, genome-wide analysis of human medulloblastoma samples by array-Comparative Genomic Hybridization (aCGH)

ABSTRACT: Medulloblastoma (MB) is the most common pediatric brain tumor and is an aggressive neoplasia arising in the cerebellum. MB includes four major histological subsets commonly subdivided in: classic, desmoplastic, anaplastic or large-cell, and nodular. The current patients risk stratification is based on the age at diagnosis (> or < 3 years at diagnosis), the extent of residual tumor mass post-operative, and disease dissemination. An average risk is assigned to patients older than 3 years of age with minimal or no tumor residual. These patients are more than 60% of overall MBs and have an overall survival between 50-70% at 5 years. It is widely accepted that tumor aggressiveness and progression depend on genetic abnormalities. We performed the genome-wide study, focused on classic MB belonging to pediatric patients at standard risk. We analyzed 31 MB samples using high resolution oligonucleotide Human Genome CGH 244K (Agilent Technologies). The present study may help to identify novel molecular prognostic markers useful to refining current criteria of patients´ relapse risk estimation in this subgroup of patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE23005 | GEO | 2011/01/01

SECONDARY ACCESSION(S): PRJNA129911

REPOSITORIES: GEO

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High-resolution, genome-wide analysis of human medulloblastoma samples by array-Comparative Genomic Hybridization (aCGH)

Project description:Medulloblastoma (MB) is the most common pediatric brain tumor and is an aggressive neoplasia arising in the cerebellum. MB includes four major histological subsets commonly subdivided in: classic, desmoplastic, anaplastic or large-cell, and nodular. The current patients risk stratification is based on the age at diagnosis (> or < 3 years at diagnosis), the extent of residual tumor mass post-operative, and disease dissemination. An average risk is assigned to patients older than 3 years of age with minimal or no tumor residual. These patients are more than 60% of overall MBs and have an overall survival between 50-70% at 5 years. It is widely accepted that tumor aggressiveness and progression depend on genetic abnormalities. We performed the genome-wide study, focused on classic MB belonging to pediatric patients at standard risk. We analyzed 31 MB samples using high resolution oligonucleotide Human Genome CGH 244K (Agilent Technologies). The present study may help to identify novel molecular prognostic markers useful to refining current criteria of patientsM-BM-4 relapse risk estimation in this subgroup of patients. We analyzed 31 samples of classic medulloblastoma from patients older than 3 years of age at diagnosis

2011-01-01 | E-GEOD-23005 | biostudies-arrayexpress

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Artificial Intelligence in proteomic profiling of Cerebrospinal fluid from extraventricular drainage in child Medulloblastoma

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Pediatric pineal germinomas: Epigenetic and genomic approach (comparative genomic hybridization)

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Pediatric pineal germinomas: Epigenetic and genomic approach (transcription profiling)

2016-11-26 | E-MTAB-5108 | biostudies-arrayexpress

DNA methylation adds prognostic value to minimal residual disease status in pediatric T-cell acute lymphoblastic leukemia

Project description:Background: Despite increased knowledge about genetic aberrations in pediatric T-cell acute lymphoblastic leukemia (T-ALL), no clinically feasible treatment-stratifying marker exists at diagnosis. Instead patients are enrolled in intensive induction therapies with substantial side effects. In modern protocols, therapy response is monitored by minimal residual disease (MRD) analysis, and used for post-induction risk group stratification. DNA methylation profiling is a candidate for subtype discrimination at diagnosis and we investigated its role as a prognostic marker in pediatric T-ALL. Procedure: Sixty-five diagnostic T-ALL samples from Nordic pediatric patients treated according to the NOPHO-ALL2008 protocol were analyzed by HumMeth450K genome wide DNA methylation arrays. Methylation status was analyzed in relation to clinical data and early T-cell precursor (ETP) phenotype. Results: Two distinct CpG Island Methylator Phenotype (CIMP) groups were identified. Patients with a CIMP negative profile had an inferior response to treatment compared to CIMP positive patients (3-year cumulative incidence of relapse (CIR3y) rate: 29% vs. 6%, p=0.01). Most importantly, CIMP classification at diagnosis allowed subgrouping of high risk T-ALL patients (MRD ≥0.1% at day 29) into two groups with significant differences in outcome (CIR3y rates: CIMP negative 50% vs CIMP positive 12%; p=0.02). These groups did not differ regarding ETP-phenotype, but the CIMP negative group was younger (p=0.02) and had higher white blood cell count at diagnosis (p=0.004) compared with the CIMP positive group. Conclusions: CIMP classification at diagnosis in combination with MRD during induction therapy is a strong candidate for further risk classification and could confer important information in treatment decision-making.

2016-03-30 | GSE69954 | GEO

Transcription profiling of human diagnostic samples from children with NCI high risk B-precursor ALL treated on the protocol COG 1961 to investigate early response and outcome in high-risk childhood acute lymphoblastic leukemia

Project description:The cure rate for childhood ALL has improved considerably in part because therapy is routinely tailored to the predicted risk of relapse. Various clinical and laboratory variables are used in current risk-stratification schemes, but many children who fail therapy lack adverse prognostic factors at initial diagnosis. Using gene expression analysis, we have identified genes and pathways in a NCI high-risk childhood B-precursor ALL cohort at diagnosis that may play a role in early blast regression as correlated with the Day 7 marrow status. We have also identified a 47-probeset signature (representing 41 unique genes) that was predictive of long term outcome in our dataset as well as three large independent datasets of childhood ALL treated on different protocols. Experiment Overall Design: Diagnostic marrow samples from 99 children with NCI high risk B-precursor ALL treated on the protocol COG 1961 were analyzed. To study genetic profiles associated with early response to therapy, 82 of the total 99 patients were analyzed: 42 patients with a M1 marrow at day 7 of therapy were compared to 40 patients with a M3 marrow at day 7. To study the genes associated with long-term outcome, expression profiles of 59 (of the total 99) patients were analyzed: 28 patients who remained in complete continuous remission (CCR) for at least 4 years and 31 patients who suffered a bone marrow relapse within the first 3 years of initial diagnosis. Forty-two patients were common in both the early response and outcome analyses.

2008-06-15 | E-GEOD-7440 | biostudies-arrayexpress

Detection of lower levels of SNAP25 using multiple microarray systems and its functional significance in medulloblastoma

Project description:Medulloblastoma (MB) is the most common pediatric malignant brain tumor and patients with a high-risk or recurrent MB respond poorly to current therapies, with higher related mortality. Potential molecules related to MB must be identified to develop targets for therapeutic development. In the present study, we compared MB microarray data obtained using different microarray systems and significant targets were selected by gene annotation and enrichment analysis. Genes for soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) annotated with the function “vesicle” were identified and one of these proteins, synaptosomal-associated protein 25 (SNAP25), had significantly lower expression levels in MB. In addition, SNAP25 was detected in a very low number of MB cells according to western blot analysis and immunohistochemical analyses of archived and formalin-fixed/paraffin-embedded human MB specimens. We found that SNAP25 could change the morphology and the chemotherapeutic effect of arabinofuranosyl cytidine (Ara-C) on SNAP25-expressing MB cells. In conclusion, the expression of SNAP25 is crucial for the dendrite formation and correlate to the targeted chemotherapy. The detection of SNAP25 expression in MB cells may be essential for the chemotherapeutic application of Ara-C.

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