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Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells

Author

Listed:
  • Zachary J. Reitman

    (Dana Farber Cancer Institute
    Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

  • Brenton R. Paolella

    (Dana Farber Cancer Institute
    Broad Institute of MIT and Harvard)

  • Guillaume Bergthold

    (Innovative Pediatric Oncology Drug Discovery
    Service Hématologie-Oncologie Pédiatrique)

  • 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
    Dana-Farber Boston Children’s Cancer and Blood Disorders Center
    Harvard Medical School)

  • 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
    Dana-Farber Boston Children’s Cancer and Blood Disorders Center
    Harvard Medical School)

  • Mario L. Suva

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital and Harvard Medical School
    Broad Institute of Harvard and MIT)

  • Aviv Regev

    (Broad Institute of MIT and Harvard
    Broad Institute of Harvard and MIT
    Koch Institute, MIT)

  • Charles D. Stiles

    (Dana Farber Cancer Institute)

  • Mark W. Kieran

    (Dana-Farber Boston Children’s Cancer and Blood Disorders Center
    Harvard Medical School
    Bristol-Myers Squibb
    Bristol-Myers Squibb)

  • Liliana Goumnerova

    (Boston Children’s Hospital)

  • Keith L. Ligon

    (Broad Institute of MIT and Harvard
    Dana Farber Cancer Institute)

  • Alex K. Shalek

    (Broad Institute of MIT and Harvard
    Massachusetts Institute of Technology
    Massachusetts Institute of Technology, and Harvard)

  • Pratiti Bandopadhayay

    (Broad Institute of MIT and Harvard
    Dana-Farber Boston Children’s Cancer and Blood Disorders Center
    Harvard Medical School)

  • Rameen Beroukhim

    (Dana Farber Cancer Institute
    Broad Institute of MIT and Harvard
    Dana-Farber Cancer Institute)

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.

Suggested Citation

  • 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, 2019. "Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11493-2
    DOI: 10.1038/s41467-019-11493-2
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    Cited by:

    1. Min Kyung Lee & Nasim Azizgolshani & Joshua A. Shapiro & Lananh N. Nguyen & Fred W. Kolling & George J. Zanazzi & Hildreth Robert Frost & Brock C. Christensen, 2024. "Identifying tumor type and cell type-specific gene expression alterations in pediatric central nervous system tumors," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Min Kyung Lee & Nasim Azizgolshani & Ze Zhang & Laurent Perreard & Fred W. Kolling & Lananh N. Nguyen & George J. Zanazzi & Lucas A. Salas & Brock C. Christensen, 2024. "Associations in cell type-specific hydroxymethylation and transcriptional alterations of pediatric central nervous system tumors," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Romain Sigaud & Thomas K. Albert & Caroline Hess & Thomas Hielscher & Nadine Winkler & Daniela Kocher & Carolin Walter & Daniel Münter & Florian Selt & Diren Usta & Jonas Ecker & Angela Brentrup & Mar, 2023. "MAPK inhibitor sensitivity scores predict sensitivity driven by the immune infiltration in pediatric low-grade gliomas," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

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