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

Science 2018 04;360(6386):331-335

Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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.

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Source
http://www.sciencemag.org/lookup/doi/10.1126/science.aao4750
Publisher Site
http://dx.doi.org/10.1126/science.aao4750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949869PMC
April 2018

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