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Gene expression data from CNS-PNETs and various other brain tumor samples

ABSTRACT: Primitive neuroectodermal tumors of the central nervous system (CNS PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children. Using DNA methylation and gene expression profiling we have demonstrated that a significant proportion of institutionally diagnosed CNS PNETs display molecular profiles indistinguishable from those of various other well defined CNS tumor entities, facilitating diagnosis and appropiate therapy for children with these tumors. From the remaining fraction of CNS PNETs, we have identified four distinct new CNS tumor entities extending to other neuroepithelial tumors, each associated with a recurrent genetic alteration and particular histopathological and clinical features. These molecular entities, designated “CNS Neuroblastoma with FOXR2 activation (CNS NB FOXR2)”, “CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT CIC)”, “CNS high grade neuroepithelial tumor with MN1 alteration (CNS HGNET MN1)”, and “CNS high grade neuroepithelial tumor with BCOR alteration (CNS HGNET BCOR)”, will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by these poorly differentiated CNS tumors.

ORGANISM(S): Homo sapiens

PROVIDER: GSE73038 | GEO | 2016/02/25

SECONDARY ACCESSION(S): PRJNA296007

REPOSITORIES: GEO

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Gene expression data from CNS-PNETs and various other brain tumor samples

Project description:Primitive neuroectodermal tumors of the central nervous system (CNS PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children. Using DNA methylation and gene expression profiling we have demonstrated that a significant proportion of institutionally diagnosed CNS PNETs display molecular profiles indistinguishable from those of various other well defined CNS tumor entities, facilitating diagnosis and appropiate therapy for children with these tumors. From the remaining fraction of CNS PNETs, we have identified four distinct new CNS tumor entities extending to other neuroepithelial tumors, each associated with a recurrent genetic alteration and particular histopathological and clinical features. These molecular entities, designated âCNS Neuroblastoma with FOXR2 activation (CNS NB FOXR2)â, âCNS Ewing sarcoma family tumor with CIC alteration (CNS EFT CIC)â, âCNS high grade neuroepithelial tumor with MN1 alteration (CNS HGNET MN1)â, and âCNS high grade neuroepithelial tumor with BCOR alteration (CNS HGNET BCOR)â, will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by these poorly differentiated CNS tumors. 182 brain tumor samples were selected for RNA extraction and hybridization on Affymetrix Affymetrix Human Genome U133 Plus 2.0 Arrays.

2016-02-25 | E-GEOD-73038 | biostudies-arrayexpress

DNA methylation data from CNS-PNETs and various other brain tumor samples

Project description:Primitive neuroectodermal tumours of the central nervous system (CNS PNETs) are highly aggressive, poorly differentiated embryonal tumours occurring predominantly in young children. Using DNA methylation and gene expression profiling we have demonstrated that a significant proportion of institutionally diagnosed CNS PNETs display molecular profiles indistinguishable from those of various other well defined CNS tumour entities, facilitating diagnosis and appropiate therapy for children with these tumours. From the remaining fraction of CNS PNETs, we have identified four distinct new CNS tumour entities extending to other neuroepithelial tumours, each associated with a recurrent genetic alteration and particular histopathological and clinical features. These molecular entities, designated â??CNS Neuroblastoma with FOXR2 activation (CNS NB FOXR2)â??, â??CNS Ewing sarcoma family tumour with CIC alteration (CNS EFT CIC)â??, â??CNS high grade neuroepithelial tumour with MN1 alteration (CNS HGNET MN1)â??, and â??CNS high grade neuroepithelial tumour with BCOR alteration (CNS HGNET BCOR)â??, will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by these poorly differentiated CNS tumours. 586 brain tumor samples were profiled using the Illumina HumanMethylation450 BeadChip (450k) array.

2016-02-25 | E-GEOD-73801 | biostudies-arrayexpress

DNA methylation data from CNS-PNETs and various other brain tumor samples

Project description:Primitive neuroectodermal tumours of the central nervous system (CNS PNETs) are highly aggressive, poorly differentiated embryonal tumours occurring predominantly in young children. Using DNA methylation and gene expression profiling we have demonstrated that a significant proportion of institutionally diagnosed CNS PNETs display molecular profiles indistinguishable from those of various other well defined CNS tumour entities, facilitating diagnosis and appropiate therapy for children with these tumours. From the remaining fraction of CNS PNETs, we have identified four distinct new CNS tumour entities extending to other neuroepithelial tumours, each associated with a recurrent genetic alteration and particular histopathological and clinical features. These molecular entities, designated “CNS Neuroblastoma with FOXR2 activation (CNS NB FOXR2)”, “CNS Ewing sarcoma family tumour with CIC alteration (CNS EFT CIC)”, “CNS high grade neuroepithelial tumour with MN1 alteration (CNS HGNET MN1)”, and “CNS high grade neuroepithelial tumour with BCOR alteration (CNS HGNET BCOR)”, will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by these poorly differentiated CNS tumours.

2016-02-25 | GSE73801 | GEO

New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

Project description:Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated “CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)”, “CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)”, “CNS high grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)”, and “CNS high grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)”, will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors.

| EGAS00001001632 | EGA

Expression profiles of Ewing family of tumors authenticate distinct molecular entities

Project description:The concept of Ewing family of tumors (EFT), characterized by FET-ETS fusions, has been recently challenged by the description of Ewing-like tumors with different gene fusions. Here we investigate the similarities and differences of FET-ETS, BCOR-CCNB3, CIC-DUX4 and EWSR1-NFATc2 tumors samples with a number of other sarcomas. Unsupervised clustering of gene expression profiles fully discriminates these four molecular entities. Specific gene signatures and pathways were further validated in model cell lines. While a clear inflammatory signature characterizes EWSR1-NFATc2 tumors, BCOR-CCNB3 and CIC-DUX4 exhibit high expression of homeobox and ETS protein families, respectively. We strongly suggest that abnormalities of chromatin remodeling may gather CIC-DUX4 and BCOR-CCNB3 tumors with rhabdoid tumors and synovial sarcomas. This dataset conains 14 CIC-DUX4 and 7 EWSR1-NFATc2 tumor samples as well as Human mesenchymal cell line expressing EWSR1-NFATc2 (duplicates) or mock treated (duplicates) and IB120 CIC-DUX4 cell line expressing an shRNA directed against CIC-DUX4 (4 replicates) or mock treated (duplicates).

2015-06-30 | E-GEOD-60740 | biostudies-arrayexpress

Expression profiles of Ewing family of tumors authenticate distinct molecular entities

2015-06-30 | GSE60740 | GEO

DNA methylation analysis of astroblastomas

Project description:Astroblastomas represent rare cerebral tumors of the central nervous system (CNS). The status of astroblastoma as a distinct molecular entity is controversial, largely because the molecular features of astroblastomas have not been comprehensively evaluated. Herein, we used methylation profiling to compare the signatures of astroblastoma to a reference cohort of brain tumor entities. We found that astroblastomas are molecularly heterogenous and share molecular features with known brain tumor entities including plexomorphic xanthoastrocytoma, high-grade neuroepithelial tumor with MN1 abnormalities, as supratentorial ependymomas with RELA fusions.

2019-03-20 | GSE125450 | GEO

Pediatric-type high-grade neuroepithelial tumors with CIC gene fusion share a common DNA methylation signature

Project description:Pediatric neoplasms in the central nervous system show an extensive clinical and molecular heterogeneity. Molecular genetic testing contributes to accurate diagnosis and enables an optimal clinical management of affected children. Unsupervised visualization of genome-wide DNA methylation array data revealed a molecularly distinct type of pediatric high-grade neuroepithelial tumor with fusions involving the capicua transcriptional repressor (CIC) gene, with the most common fusion being CIC::LEUTX. Histopathological review demonstrated a morphologically heterogeneous group of high-grade neuroepithelial tumors with positive immunostaining for markers of glial differentiation in combination with weak and focal expression of synaptophysin, CD56 and CD99. In summary, we expand the spectrum of pediatric-type tumors of the CNS by reporting a previously uncharacterized group of rare high-grade neuroepithelial tumors that share a common DNA methylation signature and recurrent gene fusions involving the transcriptional repressor CIC.

2023-03-10 | GSE223546 | GEO

Methylation profiling of adult astroblastoma

Project description:Aims and methods: astroblastoma is a rare glial brain tumor with singular morphology. Recurrent MN1-BEND2 fusions have been recently identified in most of pediatric cases. Adolescent and adult cases, however, remain molecularly poorly defined. Here, we performed clinical and molecular characterization of a retrospective cohort of 14 adult and one adolescent gliomas with astroblastic features. Results: strikingly, we found MN1 fusions a rare event in this age group (1/15). Using methylation profiling and targeted sequencing, most cases were reclassified as either pleomorphic xanthoastrocytomas (PXA) or high-grade glioma (HGG). PXA-like ABM show BRAF mutation (6/7 with V600E mutation and 1/7 with G466E mutation) and CD34 expression. Conversely, HGG-like ABM harbored specific mutations of diffuse midline glioma (2/5) or glioblastoma (3/5). These latter patients showed an unfavorable clinical course with significantly shorter overall survival (p = 0.027). MAPK pathway alterations (including FGFR fusion, BRAF and NF1 mutations) were present in 10 of 15 patients and overrepresented in the HGG group (3/5) compared to previously reported prevalence of these alterations in GBM and diffuse midline glioma. Conclusion: We suggest that astroblastoma comprises a variety of molecularly sharply defined entities. Adults’ astroblastomas harboring molecular features of PXA and HGG should be reclassified. CNS high-grade neuroepithelial tumors with MN1 alterations appears to be a truly pediatric entity and is uncommon in adult cases with a histology of astroblastoma. Astroblastic morphology in adults should thus prompt thorough molecular investigation aiming at a clear histomolecular diagnosis and identifying actionable drug targets, especially in MAPK pathway.

2019-03-22 | E-MTAB-7490 | biostudies-arrayexpress

Gene expression analysis of primitive neuroectodermal tumors

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.

2013-05-01 | GSE19404 | GEO

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