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Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells.

Publication ,  Journal Article
Reitman, ZJ; Paolella, BR; Bergthold, G; Pelton, K; Becker, S; Jones, R; Sinai, CE; Malkin, H; Huang, Y; Grimmet, L; Herbert, ZT; Sun, Y ...
Published in: Nat Commun
August 19, 2019

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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

August 19, 2019

Volume

10

Issue

1

Start / End Page

3731

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Proto-Oncogene Proteins B-raf
  • Oncogene Proteins, Fusion
  • Oligodendroglia
  • Neural Stem Cells
  • Mitogen-Activated Protein Kinases
  • Microglia
  • Mice
  • MAP Kinase Signaling System
  • Humans
 

Citation

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Reitman, Z. J., Paolella, B. R., Bergthold, G., Pelton, K., Becker, S., Jones, R., … Beroukhim, R. (2019). Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells. Nat Commun, 10(1), 3731. https://doi.org/10.1038/s41467-019-11493-2
Reitman, Zachary J., Brenton R. Paolella, Guillaume Bergthold, Kristine Pelton, Sarah Becker, Robert Jones, Claire E. Sinai, et al. “Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells.Nat Commun 10, no. 1 (August 19, 2019): 3731. https://doi.org/10.1038/s41467-019-11493-2.
Reitman ZJ, Paolella BR, Bergthold G, Pelton K, Becker S, Jones R, et al. Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells. Nat Commun. 2019 Aug 19;10(1):3731.
Reitman, Zachary J., et al. “Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells.Nat Commun, vol. 10, no. 1, Aug. 2019, p. 3731. Pubmed, doi:10.1038/s41467-019-11493-2.
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. Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells. Nat Commun. 2019 Aug 19;10(1):3731.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

August 19, 2019

Volume

10

Issue

1

Start / End Page

3731

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Proto-Oncogene Proteins B-raf
  • Oncogene Proteins, Fusion
  • Oligodendroglia
  • Neural Stem Cells
  • Mitogen-Activated Protein Kinases
  • Microglia
  • Mice
  • MAP Kinase Signaling System
  • Humans