Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells

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 () and Rameen Beroukhim ()
Additional contact information
Zachary J. Reitman: Dana Farber Cancer Institute
Brenton R. Paolella: Dana Farber Cancer Institute
Guillaume Bergthold: Innovative Pediatric Oncology Drug Discovery
Kristine Pelton: Dana Farber Cancer Institute
Sarah Becker: Dana Farber Cancer Institute
Robert Jones: Dana Farber Cancer Institute
Claire E. Sinai: Dana-Farber Boston Children’s Cancer and Blood Disorders Center
Hayley Malkin: Dana Farber Cancer Institute
Ying Huang: Dana Farber Cancer Institute
Leslie Grimmet: Dana-Farber Cancer Institute
Zachary T. Herbert: Dana-Farber Cancer Institute
Yu Sun: Dana Farber Cancer Institute
Jessica L. Weatherbee: Dana Farber Cancer Institute
John A. Alberta: Dana Farber Cancer Institute
John F. Daley: Dana-Farber Cancer Institute
Orit Rozenblatt-Rosen: Broad Institute of MIT and Harvard
Alexandra L. Condurat: Broad Institute of MIT and Harvard
Kenin Qian: Dana-Farber Boston Children’s Cancer and Blood Disorders Center
Prasidda Khadka: Dana Farber Cancer Institute
Rosalind A. Segal: Dana Farber Cancer Institute
Daphne Haas-Kogan: Dana-Farber Cancer Institute
Mariella G. Filbin: Broad Institute of MIT and Harvard
Mario L. Suva: Broad Institute of MIT and Harvard
Aviv Regev: Broad Institute of MIT and Harvard
Charles D. Stiles: Dana Farber Cancer Institute
Mark W. Kieran: Dana-Farber Boston Children’s Cancer and Blood Disorders Center
Liliana Goumnerova: Boston Children’s Hospital
Keith L. Ligon: Broad Institute of MIT and Harvard
Alex K. Shalek: Broad Institute of MIT and Harvard
Pratiti Bandopadhayay: Broad Institute of MIT and Harvard
Rameen Beroukhim: Dana Farber Cancer Institute

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11493-2

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