Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells.

Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells.

Nature communications (2019-08-21)

Zachary J Reitman, Brenton R Paolella, Guillaume Bergthold, Kristine Pelton, Sarah Becker, Robert Jones, Claire E Sinai, Hayley Malkin, Ying Huang, Leslie Grimmet, Zachary T Herbert, Yu Sun, Jessica L Weatherbee, John A Alberta, John F Daley, Orit Rozenblatt-Rosen, Alexandra L Condurat, Kenin Qian, Prasidda Khadka, Rosalind A Segal, Daphne Haas-Kogan, Mariella G Filbin, Mario L Suva, Aviv Regev, Charles D Stiles, Mark W Kieran, Liliana Goumnerova, Keith L Ligon, Alex K Shalek, Pratiti Bandopadhayay, Rameen Beroukhim

PMID31427603

摘要

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.