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.
Description
Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq. - PubMed - NCBI
%0 Journal Article
%1 Venteicher:2017:Science:28360267
%A Venteicher, A S
%A Tirosh, I
%A Hebert, C
%A Yizhak, K
%A Neftel, C
%A Filbin, M G
%A Hovestadt, V
%A Escalante, L E
%A Shaw, M L
%A Rodman, C
%A Gillespie, S M
%A Dionne, D
%A Luo, C C
%A Ravichandran, H
%A Mylvaganam, R
%A Mount, C
%A Onozato, M L
%A Nahed, B V
%A Wakimoto, H
%A Curry, W T
%A Iafrate, A J
%A Rivera, M N
%A Frosch, M P
%A Golub, T R
%A Brastianos, P K
%A Getz, G
%A Patel, A P
%A Monje, M
%A Cahill, D P
%A Rozenblatt-Rosen, O
%A Louis, D N
%A Bernstein, B E
%A Regev, A
%A Suvà, M L
%D 2017
%J Science
%K SHOULDREAD cancer-research fulltext glioma rna-seq single-cell-sequencing
%N 6332
%R 10.1126/science.aai8478
%T Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq
%U https://www.ncbi.nlm.nih.gov/pubmed/28360267
%V 355
%X 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.
@article{Venteicher:2017:Science:28360267,
abstract = {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.},
added-at = {2018-12-19T13:50:32.000+0100},
author = {Venteicher, A S and Tirosh, I and Hebert, C and Yizhak, K and Neftel, C and Filbin, M G and Hovestadt, V and Escalante, L E and Shaw, M L and Rodman, C and Gillespie, S M and Dionne, D and Luo, C C and Ravichandran, H and Mylvaganam, R and Mount, C and Onozato, M L and Nahed, B V and Wakimoto, H and Curry, W T and Iafrate, A J and Rivera, M N and Frosch, M P and Golub, T R and Brastianos, P K and Getz, G and Patel, A P and Monje, M and Cahill, D P and Rozenblatt-Rosen, O and Louis, D N and Bernstein, B E and Regev, A and Suv{\`a}, M L},
biburl = {https://www.bibsonomy.org/bibtex/26500f4c90b7de7f62142f9281f5c4116/marcsaric},
description = {Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq. - PubMed - NCBI},
doi = {10.1126/science.aai8478},
interhash = {66af2449245410fca06322e8a9bf32de},
intrahash = {6500f4c90b7de7f62142f9281f5c4116},
journal = {Science},
keywords = {SHOULDREAD cancer-research fulltext glioma rna-seq single-cell-sequencing},
month = {03},
number = 6332,
pmid = {28360267},
timestamp = {2018-12-19T13:50:32.000+0100},
title = {Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq},
url = {https://www.ncbi.nlm.nih.gov/pubmed/28360267},
volume = 355,
year = 2017
}