Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq
Broad Institute · Harvard University · +8 more institutions
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…
Citation impact
- FWCI
- 39.13
- Percentile
- 100%
- References
- 31
Authors
34- ASAndrew S. VenteicherCorresponding
Broad Institute, Harvard University, Massachusetts General Hospital, Center for Cancer Research
- ITItay TiroshCorresponding
Broad Institute
- CHChristine Hebert
Broad Institute, Harvard University, Massachusetts General Hospital, Center for Cancer Research
- KYKeren Yizhak
Broad Institute, Harvard University, Massachusetts General Hospital, Center for Cancer Research
- CNCyril Neftel
Broad Institute, Harvard University, University Hospital of Lausanne, Massachusetts General Hospital, Center for Cancer Research
Topics & keywords
- Isocitrate dehydrogenase
- Biology
- Oligodendroglioma
- IDH1
- Glioma
- Mutant
- RNA
- Phenotype
Funding
- HHHoward Hughes Medical InstituteAward: award284347
- ACAmerican Cancer SocietyAward: award284352
- RARichard and Susan Smith Family Foundation
- VFV Foundation for Cancer ResearchAward: award284349
- ABAmerican Brain Tumor AssociationAward: award284350
- NRNeurosurgery Research and Education FoundationAward: award284351
- CICalifornia Institute of Regenerative Medicine
- BIBroad InstituteAward: Broadnext10
- KIKoch Institute for Integrative Cancer Research, Massachusetts Institute of TechnologyAward: P30-CA14051
- NINational Institutes of HealthAwards: NS065743, 1S10RR023440-01A1, K12CA090354, P30-CA14051, award284346, P50CA165962
- LCLudwig Center at Harvard
- NCNational Cancer InstituteAwards: R33CA202820, award284348, P50CA165962, P30-CA14051, CA14051, 1U24CA180922, K12CA090354