Back to Search
Start Over
Single-cell sequencing maps gene expression to mutational phylogenies in PDGF- and EGF-driven gliomas.
- Source :
-
Molecular Systems Biology . Nov2016, Vol. 12 Issue 11, pn/a-N.PAG. 17p. - Publication Year :
- 2016
-
Abstract
- Glioblastoma multiforme ( GBM) is the most common and aggressive type of primary brain tumor. Epidermal growth factor ( EGF) and platelet-derived growth factor ( PDGF) receptors are frequently amplified and/or possess gain-of-function mutations in GBM. However, clinical trials of tyrosine-kinase inhibitors have shown disappointing efficacy, in part due to intra-tumor heterogeneity. To assess the effect of clonal heterogeneity on gene expression, we derived an approach to map single-cell expression profiles to sequentially acquired mutations identified from exome sequencing. Using 288 single cells, we constructed high-resolution phylogenies of EGF-driven and PDGF-driven GBMs, modeling transcriptional kinetics during tumor evolution. Descending the phylogenetic tree of a PDGF-driven tumor corresponded to a progressive induction of an oligodendrocyte progenitor-like cell type, expressing pro-angiogenic factors. In contrast, phylogenetic analysis of an EGFR-amplified tumor showed an up-regulation of pro-invasive genes. An in-frame deletion in a specific dimerization domain of PDGF receptor correlates with an up-regulation of growth pathways in a proneural GBM and enhances proliferation when ectopically expressed in glioma cell lines. In-frame deletions in this domain are frequent in public GBM data. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 17444292
- Volume :
- 12
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Molecular Systems Biology
- Publication Type :
- Academic Journal
- Accession number :
- 119806184
- Full Text :
- https://doi.org/10.15252/msb.20166969