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

Mariella G. Filbin(Broad Institute), Itay Tirosh(Broad Institute), Volker Hovestadt(Broad Institute), McKenzie Shaw(Broad Institute), Leah E. Escalante(Broad Institute), Nathan D. Mathewson(Harvard University), Cyril Neftel(Broad Institute), Nelli Frank(St Anna Children's Hospital), Kristine Pelton(Brigham and Women's Hospital), Christine Hebert(Broad Institute), Christine Haberler(Medical University of Vienna), Keren Yizhak(Broad Institute), Johannes Gojo(Medical University of Vienna), Kristóf Égervári(Harvard University), Christopher Mount(Stanford University), Peter van Galen(Broad Institute), Dennis M. Bonal(Dana-Farber Cancer Institute), Quang‐Dé Nguyen(Dana-Farber Cancer Institute), Alexander Beck(Harvard University), Claire Sinai(Brigham and Women's Hospital), Thomas Czech(Medical University of Vienna), Christian Dorfer(Medical University of Vienna), Liliana Goumnerova(Dana-Farber/Boston Children's Cancer and Blood Disorders Center), Cinzia Lavarino(Hospital Sant Joan de Déu Barcelona), Ángel M. Carcaboso(Hospital Sant Joan de Déu Barcelona), Jaume Mora(Hospital Sant Joan de Déu Barcelona), Ravindra Mylvaganam(Harvard University), Christina C. Luo(Harvard University), Andreas Peyrl(Medical University of Vienna), Mara Popović(University of Ljubljana), Amedeo A. Azizi(Medical University of Vienna), Tracy T. Batchelor(Harvard University), Matthew P. Frosch(Harvard University), Maria Martinez‐Lage(Harvard University), Mark W. Kieran(Dana-Farber/Boston Children's Cancer and Blood Disorders Center), Pratiti Bandopadhayay(Broad Institute), Rameen Beroukhim(Broad Institute), G. Fritsch(St Anna Children's Hospital), Gad Getz(Broad Institute), Orit Rozenblatt–Rosen(Broad Institute), Kai W. Wucherpfennig(Harvard University), David N. Louis(Harvard University), Michelle Monje(Stanford University), Irene Slavc(Medical University of Vienna), Keith L. Ligon(Broad Institute), Todd R. Golub(Broad Institute), Aviv Regev(Broad Institute), B Bernstein(Broad Institute), Mario L. Suvà(Broad Institute)
Science
April 20, 2018
10.1126/science.aao4750
Cited by 730Open Access
Full Text

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

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