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

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

Nature communications (2022-04-21)
Norman L Lehman, Nathalie Spassky, Müge Sak, Amy Webb, Cory T Zumbar, Aisulu Usubalieva, Khaled J Alkhateeb, Joseph P McElroy, Kirsteen H Maclean, Paolo Fadda, Tom Liu, Vineela Gangalapudi, Jamie Carver, Zied Abdullaev, Cynthia Timmers, John R Parker, Christopher R Pierson, Bret C Mobley, Murat Gokden, Eyas M Hattab, Timothy Parrett, Ralph X Cooke, Trang D Lehman, Stefan Costinean, Anil Parwani, Brian J Williams, Randy L Jensen, Kenneth Aldape, Akshitkumar M Mistry
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-β-Actin antibody produced in mouse, clone AC-74, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Anti-MAP3K5 Antibody, clone 2E4, ascites fluid, clone 2E4, from mouse