Quick submit: 2017-02-07T23:04:35-0500
Effects of the tumor microenvironmentGlioma brain tumors that carry mutant copies of the IDH gene can be subdivided into two major classes. However, the development of and differences between these two classes are not well characterized. Venteicher et al. coupled bulk sequencing and publicly available data with single-cell RNA sequencing data on glioma patient tissue samples. They identified a common lineage program that is shared between glioma subtypes. This suggests that the observed differences between the two glioma classes originate from lineage-specific genetic changes and the tumor microenvironment.Science, this issue p. eaai8478 Tumor subclasses differ according to the genotypes and phenotypes of malignant cells as well as the composition of the tumor microenvironment (TME). We dissected these influences in isocitrate dehydrogenase (IDH)-mutant gliomas by combining 14,226 single-cell RNA sequencing (RNA-seq) profiles from 16 patient samples with bulk RNA-seq profiles from 165 patient samples. Differences in bulk profiles between IDH-mutant astrocytoma and oligodendroglioma can be primarily explained by distinct TME and signature genetic events, whereas both tumor types share similar developmental hierarchies and lineages of glial differentiation. As tumor grade increases, we find enhanced proliferation of malignant cells, larger pools of undifferentiated glioma cells, and an increase in macrophage over microglia expression programs in TME. Our work provides a unifying model for IDH-mutant gliomas and a general framework for dissecting the differences among human tumor subclasses.
Macrophages ; Astrocytoma ; Oligodendroglioma ; Isocitrate Dehydrogenase ; Genotypes ; Microglia ; Idh Gene ; Brain Tumors ; Differentiation ; RNA ; Glioma Cells ; Microenvironments ; Glioma ; Cell Proliferation ; Development & Cell Cycle ; Neurogenetics;
Venteicher, Andrew S., Itay Tirosh, Christine Hebert, Keren Yizhak, Cyril Neftel, Mariella G. Filbin, Volker Hovestadt, et al. 2017. “Decoupling Genetics, Lineages, and Microenvironment in IDH-Mutant Gliomas by Single-Cell RNA-Seq.” Science 355 (6332) (March 30): eaai8478. doi:10.1126/science.aai8478.
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