Array-CGH screening of supratentorial primitive neuroectodermal tumors (stPNETs)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE8736 | GEO | 2007/08/10
SECONDARY ACCESSION(S): PRJNA101999
REPOSITORIES: GEO
Similar Datasets
Project description:Medulloblastomas and supratentorial primitive neuroectodermal tumors are aggressive childhood tumors. We report our findings using array comparative genomic hybridization (CGH) on a whole-genome BAC/PAC/cosmid array with a median clone separation of 0.97 Mb to study 34 medulloblastomas and 7 supratentorial primitive neuroectodermal tumors. Array CGH allowed identification and mapping of numerous novel, small regions of copy number change to genomic sequence in addition to the large regions already known from previous studies. Novel amplifications were identified, some encompassing oncogenes MYCL1, PDGFRA, KIT, and MYB not previously reported to show amplification in these tumors. In addition, one supratentorial primitive neuroectodermal tumor had lost both copies of the tumor-suppressor genes CDKN2A and CDKN2B. Ten medulloblastomas had findings suggestive of isochromosome 17q. In contrast to previous reports using conventional CGH, array CGH identified 3 distinct breakpoints in these cases: Ch 17: 17940393-19251679 (17p11.2, n = 6), Ch 17: 20111990-23308272 (17p11.2-17q11.2, n = 4), and Ch 17: 38425359-39091575 (17q21.31, n = 1). Significant differences were found in the patterns of copy number change between medulloblastomas and supratentorial primitive neuroectodermal tumors, providing further evidence that these tumors are genetically distinct despite their morphologic and behavioral similarities.
| S-EPMC2816352 | biostudies-literature
Project description:DNA copy-number profiling of 80 primary medulloblastomas of different histologies Keywords: Genetic modification
2007-08-01 | GSE8634 | GEO
Project description:DNA copy-number profiling of 80 primary medulloblastomas of different histologies Keywords: Genetic modification Comparison of tumor DNA (medulloblastoma) versus control DNA (pool of lymphocyte DNA from 10 healthy donors). Whole-genome screening for DNA copy-number aberrations using array-based comparative genomic hybridization (aCGH). Tumor DNA labeled in Cy3 and control DNA labeled in Cy5.
2007-08-01 | E-GEOD-8634 | biostudies-arrayexpress
Project description:Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are a rare group of neoplasms occurring in the CNS that includes supratentorial CNS-PNETs, medulloepitheliomas, and ependymoblastomas. While ependymoblastomas frequently carry chromosome 19q13.41 amplification and show aggressive clinical behavior, the biological mechanisms and molecular alterations contributing to the pathogenesis of supratentorial CNS-PNETs remain poorly understood. Moreover, genetic alterations suitable for molecular risk stratification are undefined to date.In order to identify possible molecular markers, we performed multiplex ligation-dependent probe amplification (MLPA) and molecular inversion probe (MIP) analysis on DNA samples of 25 supratentorial CNS-PNETs (median age, 5.35 years; range, 2.41–17.28 years). Tumors with ependymoblastic rosettes (ependymoblastoma/ETANTR) and LIN28A positivity were excluded.MLPA and MIP analysis revealed large losses of genomic material of chromosomes 3, 4, 5, and 13, while frequent gains affected chromosomes 1, 17, 19, 20, and 22. High copy number gains (amplifications) were found in particular at chromosomes 2p24.3 (MYCN, n = 6 cases) and 4q12 (n = 2 cases). Patients with tumors harboring 2p gain or MYCN amplification showed unfavorable overall survival (P = .003 and P = .001, respectively).These markers were independent of the presence of metastases, which was indeed a clinical factor associated with poor overall survival (P = .01) in this series.In the era of the personalized neuro-oncology, the identification of these molecular prognostic markers associated with patient outcome may represent a significant step towards improved patient stratification and risk-adapted therapeutic strategies for patients suffering from supratentorial CNS-PNETs.
| S-EPMC4057132 | biostudies-literature
Project description:DNA copy-number profiling of 73 T-ALLs Keywords: Genetic modification Comparison of tumor DNA (tumor) versus control DNA (pool of lymphocyte DNA from 10 healthy donors). Whole-genome screening for DNA copy-number aberrations using array-based comparative genomic hybridization (aCGH). Tumor DNA labeled in Cy3 and control DNA labeled in Cy5.
2007-08-25 | E-GEOD-8738 | biostudies-arrayexpress
Project description:DNA copy-number profiling of 73 T-ALLs Keywords: Genetic modification
2007-08-25 | GSE8738 | GEO
Project description:DNA copy-number profiling of 66 astrocytomas of WHO °I or °II Keywords: Genetic modification
2007-08-10 | GSE8737 | GEO
Project description:Central nervous system primitive neuroectodermal tumors (CNS PNET) and medulloblastomas are both embryonal tumors that predominantly occur in children. We used microarrays to analyse a cohort of CNS PNETs and medulloblastomas to identify gene expression related to tumor subgroups. RNA extracted from 23 frozen tumor samples, plus a commercial fetal brain sample, was analysed using Affymetrix U133 plus 2.0 arrays. Tumour subgroups, based on gene expression, were identified using clustering methods.
| S-ECPF-GEOD-19404 | biostudies-other
Project description:BackgroundSupratentorial PNETs (sPNET) are uncommon embryonal malignancies of the central nervous system whose prognosis has historically been poor. We evaluated the outcome and prognostic factors of children with sPNET treated prospectively on a Children's Oncology Group trial.ProcedureFollowing surgery, patients received craniospinal radiotherapy with concurrent carboplatin followed by six months of maintenance chemotherapy with cyclophosphamide and vincristine.ResultsFive-year overall survival (OS) and progression-free survival (PFS) for all patients was 58 ± 7% and 48 ± 7%. For patients with pineoblastoma (n = 23), five-year OS and PFS was 81 ± 9% and 62 ± 11%. Extent of resection but not M-stage was prognostic. Five-year OS and PFS for 37 patients with non-pineal tumors (NPsPNET) was 44 ± 8% and 39 ± 8%, significantly worse than for PB (P = 0.055 and 0.009 respectively). Extent of resection and major radiotherapy deviations were prognostic. Five year OS was 59 +/- 11.4% for those undergoing complete resection versus 10.4 +/- 7% for those who did not (P = 0.017). Central pathologic review called 14 (38%) "classic" sPNET, 8 (22%) "undifferentiated" and 13 (35%) "malignant gliomas." There was no significant difference between the subgroups, although survival distributions approached significance when the combined "classic" and "undifferentiated" group was compared to the "malignant gliomas."ConclusionsCarboplatin during RT followed by 6 months of non-intensive chemotherapy is a feasible treatment strategy for patients with sPNET. Aggressive surgical resection should be attempted if feasible. The classification of supratentorial small cell malignancies can be difficult.
| S-EPMC4376578 | biostudies-literature
Project description:Purpose:This study aimed to explore significant genes and pathways involved in the pathogenesis of supratentorial primitive neuroectodermal tumor (sPNET). Materials and methods:Gene expression profile of GSE14295 was downloaded from publicly available Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened out in primary sPNET samples compared with normal fetal and adult brain reference samples (sPNET vs fetal brain and sPNET vs adult brain). Pathway enrichment analysis of these DEGs was conducted, followed by protein-protein interaction (PPI) network construction and significant module selection. Additionally, transcription factors (TFs) regulating the common DEGs in the two comparison groups were identified, and the regulatory network was constructed. Results:In total, 526 DEGs (99 up- and 427 downregulated) in sPNET vs fetal brain and 815 DEGs (200 up- and 615 downregulated) in sPNET vs adult brain were identified. DEGs in sPNET vs fetal brain and sPNET vs adult brain were associated with calcium signaling pathway, cell cycle, and p53 signaling pathway. CDK1, CDC20, BUB1B, and BUB1 were hub nodes in the PPI networks of DEGs in sPNET vs fetal brain and sPNET vs adult brain. Significant modules were extracted from the PPI networks. In addition, 64 upregulated and 200 downregulated overlapping DEGs were identified in both sPNET vs fetal brain and sPNET vs adult brain. The genes involved in the regulatory network upon overlapping DEGs and the TFs were correlated with calcium signaling pathway. Conclusion:Calcium signaling pathway and several genes (CDK1, CDC20, BUB1B, and BUB1) may play important roles in the pathogenesis of sPNET.
| S-EPMC5894672 | biostudies-literature