1. Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells.
- Author
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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, and Beroukhim R
- Subjects
- Animals, Brain Neoplasms genetics, Humans, MAP Kinase Signaling System genetics, Mice, Microglia pathology, Mitogen-Activated Protein Kinases genetics, Mitogen-Activated Protein Kinases metabolism, Oligodendroglia cytology, Oncogene Proteins, Fusion metabolism, Tumor Cells, Cultured, Astrocytoma genetics, Astrocytoma pathology, Brain Neoplasms pathology, Neural Stem Cells cytology, Proto-Oncogene Proteins B-raf genetics
- Abstract
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.
- Published
- 2019
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