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

Author:

Filbin Mariella G.12345ORCID,Tirosh Itay346ORCID,Hovestadt Volker134ORCID,Shaw McKenzie L.134,Escalante Leah E.134,Mathewson Nathan D.7ORCID,Neftel Cyril1348,Frank Nelli9,Pelton Kristine10,Hebert Christine M.134,Haberler Christine11,Yizhak Keren4,Gojo Johannes5ORCID,Egervari Kristof1ORCID,Mount Christopher12,van Galen Peter134,Bonal Dennis M.13ORCID,Nguyen Quang-De13ORCID,Beck Alexander1,Sinai Claire210ORCID,Czech Thomas14ORCID,Dorfer Christian14ORCID,Goumnerova Liliana2,Lavarino Cinzia15,Carcaboso Angel M.15ORCID,Mora Jaume15,Mylvaganam Ravindra1ORCID,Luo Christina C.1ORCID,Peyrl Andreas5ORCID,Popović Mara16,Azizi Amedeo5ORCID,Batchelor Tracy T.17,Frosch Matthew P.1ORCID,Martinez-Lage Maria1ORCID,Kieran Mark W.2ORCID,Bandopadhayay Pratiti24ORCID,Beroukhim Rameen418ORCID,Fritsch Gerhard9,Getz Gad14ORCID,Rozenblatt-Rosen Orit34ORCID,Wucherpfennig Kai W.7ORCID,Louis David N.1ORCID,Monje Michelle12ORCID,Slavc Irene5ORCID,Ligon Keith L.2410ORCID,Golub Todd R.24ORCID,Regev Aviv3419ORCID,Bernstein Bradley E.134ORCID,Suvà Mario L.134ORCID

Affiliation:

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. Department of Biology, Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, MIT, Cambridge, MA 02139, USA.

Abstract

The cellular composition of H3K27M gliomas Diffuse midline gliomas with histone H3 lysine27-to-methionine mutations (H3K27M-glioma) are an aggressive type of childhood cancer with few options for treatment. Filbin et al. used a single-cell sequencing approach to study the oncogenic programs, genetics, and cellular hierarchies of H3K27M-glioma. Tumors were mainly composed of cells resembling oligodendrocyte precursor cells, whereas differentiated malignant cells were a smaller fraction. In comparison with other gliomas, these cancers had distinct oncogenic programs and stem cell–like profiles that contributed to their stable tumor-propagating potential. The analysis also identified a lineage-specific marker that may be useful in developing therapies. Science , this issue p. 331

Funder

Howard Hughes Medical Institute

NIH Office of the Director

National Cancer Institute

Richard and Susan Smith Family Foundation

alexslemonade

The V Foundation

The Cure Starts Now

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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