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Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes [Nanostring]

ABSTRACT: Astroblastoma (AB) is an unusual brain tumor of unknown origin. We performed a clinicogenomic analysis of AB-like tumors.

ORGANISM(S): Homo sapiens

PROVIDER: GSE196697 | GEO | 2022/02/20

REPOSITORIES: GEO

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Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes.

Project description:Astroblastoma (AB) is an unusual brain tumor of unknown origin. We performed an integrated clinicogenomic analysis of 36 AB-like tumors. Lesions with MN1-BEND2 fusions demonstrated decreased promoter methylation and increased expression of IGF2-H19 and DLK1-DIO3 imprinted region genes. They also relatively overexpressed genes highly expressed during fetal brain development prior to 25 post-conception weeks (pcw), including genes enriched in ventricular zone radial glia (vRG), and generally presented in young children. Other tumors highly expressed MAP kinase pathway, PI3K pathway and X-inactivation escape genes. These and a third group of tumors tended to occur in young adults and showed enriched expression of outer radial glia (oRG) and truncated radial glia (tRG) genes, and genes highly expressed after 25 pcw. Many of the latter are involved in axonal migration or synaptic plasticity and are implicated in autism, schizophrenia and other cognitive disorders. Findings suggest that AB-like tumors arise in the context of epigenetic and genetic changes in neural progenitors during fetal and later brain development: early ependymal tumors with MN1-BEND2 fusions (EET-MN1) from vRG-derived progenitor cells, and MAPK/PI3K and classic astroblastomas from oRG- and tRG-derived progenitors, respectively. Lastly, we found that like EET-MN1, immature ependymal cells express IGF2 and may represent an important source of this growth factor in the fetal lateral ventricular zone neural stem cell niche.

2022-02-20 | GSE165351 | GEO

Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes [methylation]

2022-02-20 | GSE166569 | GEO

Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes [Affymetrix]

2022-02-20 | GSE165813 | GEO

Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes.

Project description:Astroblastomas (ABs) are rare brain tumors of unknown origin. We performed an integrative genetic and epigenetic analysis of AB-like tumors. Here, we show that tumors traceable to neural stem/progenitor cells (radial glia) that emerge during early to later brain development occur in children and young adults, respectively. Tumors with MN1-BEND2 fusion appear to present exclusively in females and exhibit overexpression of genes expressed prior to 25 post-conception weeks (pcw), including genes enriched in early ventricular zone radial glia and ependymal tumors. Other, histologically classic ABs overexpress or harbor mutations of mitogen-activated protein kinase pathway genes, outer and truncated radial glia genes, and genes expressed after 25 pcw, including neuronal and astrocyte markers. Findings support that AB-like tumors arise in the context of epigenetic and genetic changes in neural progenitors. Selective gene fusion, variable imprinting and/or chromosome X-inactivation escape resulting in biallelic overexpression may contribute to female predominance of AB molecular subtypes.

| S-EPMC9018799 | biostudies-literature

Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes [Nanostring]

Project description:Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes [Nanostring]

| PRJNA806894 | ENA

Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes.

Project description:Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes.

| PRJNA694144 | ENA

Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes [Affymetrix]

Project description:Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes [Affymetrix]

| PRJNA697956 | ENA

Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes [methylation]

Project description:Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes [methylation]

| PRJNA701290 | ENA

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

Radial glia and radial glia-like cells: Their role in neurogenesis and regeneration

Project description:Radial glia is a cell type traditionally associated with the developing nervous system, particularly with the formation of cortical layers in the mammalian brain. Nonetheless, some of these cells, or closely related types, called radial glia-like cells are found in adult central nervous system structures, functioning as neurogenic progenitors in normal homeostatic maintenance and in response to injury. The heterogeneity of radial glia-like cells is nowadays being probed with molecular tools, primarily by the expression of specific genes that define cell types. Similar markers have identified radial glia-like cells in the nervous system of non-vertebrate organisms. In this review, we focus on adult radial glia-like cells in neurogenic processes during homeostasis and in response to injury. We highlight our results using a non-vertebrate model system, the echinoderm Holothuria glaberrima where we have described a radial glia-like cell that plays a prominent role in the regeneration of the holothurian central nervous system.

| S-EPMC9708897 | biostudies-literature

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