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Science. 2018 Apr 20;360(6386):331-335. doi: 10.1126/science.aao4750.

Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq.

Author information

1
Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
2
Department of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA.
3
Klarman Cell Observatory, Broad Institute of Harvard and Massachussetts Institute of Technology (MIT), Cambridge, MA 02142, USA.
4
Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
5
Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
6
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
7
Department of Cancer Immunology and Virology, Department of Microbiology and Immunobiology, Department of Neurology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
8
Institute of Pathology, Faculty of Biology and Medicine, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland.
9
Children's Cancer Research Institute (CCRI), St. Anna Kinderspital, Medical University of Vienna, Vienna, Austria.
10
Department of Oncologic Pathology, Brigham and Women's Hospital, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
11
Institute of Neurology, Medical University of Vienna, Vienna, Austria.
12
Departments of Neurology, Neurosurgery, Pediatrics, and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
13
Center for Biomedical Imaging in Oncology, Lurie Family Imaging Center, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
14
Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.
15
Developmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, Esplugues de Llobregat, 08950 Barcelona, Spain.
16
Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
17
Departments of Neurology and Radiation Oncology, Division of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, USA.
18
Departments of Cancer Biology and Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, USA.
19
Klarman Cell Observatory, Broad Institute of Harvard and Massachussetts Institute of Technology (MIT), Cambridge, MA 02142, USA. suva.mario@mgh.harvard.edu bernstein.bradley@mgh.harvard.edu aregev@broadinstitute.org.
20
Department of Biology, Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, MIT, Cambridge, MA 02139, USA.
21
Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. suva.mario@mgh.harvard.edu bernstein.bradley@mgh.harvard.edu aregev@broadinstitute.org.

Abstract

Gliomas with histone H3 lysine27-to-methionine mutations (H3K27M-glioma) arise primarily in the midline of the central nervous system of young children, suggesting a cooperation between genetics and cellular context in tumorigenesis. Although the genetics of H3K27M-glioma are well characterized, their cellular architecture remains uncharted. We performed single-cell RNA sequencing in 3321 cells from six primary H3K27M-glioma and matched models. We found that H3K27M-glioma primarily contain cells that resemble oligodendrocyte precursor cells (OPC-like), whereas more differentiated malignant cells are a minority. OPC-like cells exhibit greater proliferation and tumor-propagating potential than their more differentiated counterparts and are at least in part sustained by PDGFRA signaling. Our study characterizes oncogenic and developmental programs in H3K27M-glioma at single-cell resolution and across genetic subclones, suggesting potential therapeutic targets in this disease.

PMID:
29674595
PMCID:
PMC5949869
[Available on 2019-04-20]
DOI:
10.1126/science.aao4750
[Indexed for MEDLINE]

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