Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells.

Journal Article (Journal Article)

Pilocytic astrocytoma (PA), the most common childhood brain tumor, is a low-grade glioma with a single driver BRAF rearrangement. Here, we perform scRNAseq in six PAs using methods that enabled detection of the rearrangement. When compared to higher-grade gliomas, a strikingly higher proportion of the PA cancer cells exhibit a differentiated, astrocyte-like phenotype. A smaller proportion of cells exhibit a progenitor-like phenotype with evidence of proliferation. These express a mitogen-activated protein kinase (MAPK) programme that was absent from higher-grade gliomas. Immune cells, especially microglia, comprise 40% of all cells in the PAs and account for differences in bulk expression profiles between tumor locations and subtypes. These data indicate that MAPK signaling is restricted to relatively undifferentiated cancer cells in PA, with implications for investigational therapies directed at this pathway.

Full Text

Duke Authors

Cited Authors

  • Reitman, ZJ; Paolella, BR; Bergthold, G; Pelton, K; Becker, S; Jones, R; Sinai, CE; Malkin, H; Huang, Y; Grimmet, L; Herbert, ZT; Sun, Y; Weatherbee, JL; Alberta, JA; Daley, JF; Rozenblatt-Rosen, O; Condurat, AL; Qian, K; Khadka, P; Segal, RA; Haas-Kogan, D; Filbin, MG; Suva, ML; Regev, A; Stiles, CD; Kieran, MW; Goumnerova, L; Ligon, KL; Shalek, AK; Bandopadhayay, P; Beroukhim, R

Published Date

  • August 19, 2019

Published In

Volume / Issue

  • 10 / 1

Start / End Page

  • 3731 -

PubMed ID

  • 31427603

Pubmed Central ID

  • PMC6700116

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-019-11493-2

Language

  • eng

Conference Location

  • England