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Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq.
Venteicher, Andrew S; Tirosh, Itay; Hebert, Christine; Yizhak, Keren; Neftel, Cyril; Filbin, Mariella G; Hovestadt, Volker; Escalante, Leah E; Shaw, McKenzie L; Rodman, Christopher; Gillespie, Shawn M; Dionne, Danielle; Luo, Christina C; Ravichandran, Hiranmayi; Mylvaganam, Ravindra; Mount, Christopher; Onozato, Maristela L; Nahed, Brian V; Wakimoto, Hiroaki; Curry, William T; Iafrate, A John; Rivera, Miguel N; Frosch, Matthew P; Golub, Todd R; Brastianos, Priscilla K; Getz, Gad; Patel, Anoop P; Monje, Michelle; Cahill, Daniel P; Rozenblatt-Rosen, Orit; Louis, David N; Bernstein, Bradley E; Regev, Aviv; Suvà, Mario L.
Affiliation
  • Venteicher AS; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Tirosh I; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Hebert C; Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Yizhak K; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. suva.mario@mgh.harvard.edu aregev@broadinstitute.org tirosh@broadinstitute.org.
  • Neftel C; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Filbin MG; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Hovestadt V; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Escalante LE; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Shaw ML; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Rodman C; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Gillespie SM; Institute of Pathology, Faculty of Biology and Medicine, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland.
  • Dionne D; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Luo CC; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Ravichandran H; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Children's Hospital Cancer Center, Boston, MA 02215, USA.
  • Mylvaganam R; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Mount C; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Onozato ML; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Nahed BV; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Wakimoto H; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Curry WT; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Iafrate AJ; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Rivera MN; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Frosch MP; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Golub TR; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Brastianos PK; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Getz G; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Patel AP; Departments of Neurology, Neurosurgery, Pediatrics and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Monje M; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Cahill DP; Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Rozenblatt-Rosen O; Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Louis DN; Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Bernstein BE; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Regev A; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Suvà ML; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Science ; 355(6332)2017 03 31.
Article in En | MEDLINE | ID: mdl-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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain Neoplasms / Tumor Microenvironment / Glioma / Isocitrate Dehydrogenase Type of study: Prognostic_studies Limits: Humans Language: En Journal: Science Year: 2017 Document type: Article Affiliation country:
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain Neoplasms / Tumor Microenvironment / Glioma / Isocitrate Dehydrogenase Type of study: Prognostic_studies Limits: Humans Language: En Journal: Science Year: 2017 Document type: Article Affiliation country: