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Science DOI:10.1126/science.aao4750

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

Publication TypeJournal Article
Year of Publication2018
AuthorsFilbin, MG, Tirosh, I, Hovestadt, V, Shaw, MKL, Escalante, LE, Mathewson, ND, Neftel, C, Frank, N, Pelton, K, Hebert, CM, Haberler, C, Yizhak, K, Gojo, J, Egervari, K, Mount, C, van Galen, P, Bonal, DM, De Nguyen, Q-, Beck, A, Sinai, C, Czech, T, Dorfer, C, Goumnerova, L, Lavarino, C, Carcaboso, AM, Mora, J, Mylvaganam, R, Luo, CC, Peyrl, A, Popović, M, Azizi, A, Batchelor, TT, Frosch, MP, Martinez-Lage, M, Kieran, MW, Bandopadhayay, P, Beroukhim, R, Fritsch, G, Getz, G, Rozenblatt-Rosen, O, Wucherpfennig, KW, Louis, DN, Monje, M, Slavc, I, Ligon, KL, Golub, TR, Regev, A, Bernstein, BE, Suvà, ML
Date Published2018 04 20
KeywordsBrain Neoplasms, Carcinogenesis, Cell Proliferation, Glioma, Histones, Humans, Mitogen-Activated Protein Kinase 7, Mutation, Oligodendroglia, Oncogenes, Receptor, Platelet-Derived Growth Factor alpha, Sequence Analysis, RNA, Single-Cell Analysis

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 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.


Alternate JournalScience
PubMed ID29674595
PubMed Central IDPMC5949869
Grant ListR01 CA188228 / CA / NCI NIH HHS / United States
DP1 CA216873 / CA / NCI NIH HHS / United States
U24 CA180922 / CA / NCI NIH HHS / United States
/ HHMI / Howard Hughes Medical Institute / United States
P30 CA014051 / CA / NCI NIH HHS / United States
P01 CA142536 / CA / NCI NIH HHS / United States
K12 CA090354 / CA / NCI NIH HHS / United States
S10 RR023440 / RR / NCRR NIH HHS / United States
R33 CA202820 / CA / NCI NIH HHS / United States
R01 CA215489 / CA / NCI NIH HHS / United States
R01 CA219943 / CA / NCI NIH HHS / United States
P50 CA165962 / CA / NCI NIH HHS / United States