Gene expression data from NRAS-driven CNS-PNET zebrafish brain tumors and normal brain.
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ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE80768 | GEO | 2016/09/12
SECONDARY ACCESSION(S): PRJNA319956
REPOSITORIES: GEO
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Project description:Recently, we described a new animal model of CNS primitive neuroectodermal tumors (CNS-PNET), which was generated by orthotopic transplantation of human Radial Glial (RG) cells into NOD-SCID mice’s brain sub- ventricular zone. In the current study we conducted comprehensive RNA-Seq analyses to gain some insights on the mechanisms underlying tumorigenesis in this mouse model of CNS-PNET. Here we show that the RNA-Seq profiles derived from these tumors cluster with those reported for patients’ PNETs.
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Project description:Gene expression data from NRAS-driven CNS-PNET zebrafish brain tumors and normal brain.
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Project description:In our study we aimed to define CNS-PNET subgroups. We performed Expression, Genotyping and/or Immunohistochemistry on 142 samples from 20 worldwide centers. Using these techniques, we have identified three molecular subgroups with distinct expression and copy number patterns, as well as, unique clinical characteristics. Specifically, these molecular subgroups were distinguished by primitive neural (group 1), oligoneural (group 2), and mesenchymal lineage (group 3) gene-expression signatures with differential expression of cell-lineage markers LIN28 and OLIG2. Our report underscores the importance of concerted, collaborative efforts to study large retrospective cohorts of tumours and patients to accelerate biological and ultimately therapeutic studies of rare tumours. The outcome of such a collaboration allowed us to identify LIN28 and OLIG2 as promising diagnostic and prognostic molecular markers for CNS PNET that warrant further assessment in prospective clinical trials.
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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.
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