Comparison of EGF and PDGF driven glioblastomas.
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 these tumors. Despite years of research into tyrosine-kinase inhibitors, clinical trials have shown disappointing efficacy. One of the underlying reasons is intra-tumor heterogeneity. To assess the effect of intra-tumor heterogeneity on gene expression, we derived a general 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. A deletion in a PDGF-receptor domain involved in dimerization correlated to an up-regulation of the PI3K/AKT pathway in a proneural GBM, and ectopic expression of this mutant PDGFRA in vitro enhanced proliferation and invasiveness. Descending the phylogenetic tree of the PDGFR-driven tumor corresponded to a progressive induction of an oligodendrocyte progenitor-like cell type that expresses growth and angiogenic factors. In contrast, phylogenetic analysis of an EGFR-amplified tumor showed a gradual up-regulation of pro-invasive genes.
- Type: Other
- Archiver: European Genome-Phenome Archive (EGA)
Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data
Dataset ID | Description | Technology | Samples |
---|---|---|---|
EGAD00001002269 | Illumina HiSeq 4000 | 1 | |
EGAD00001002270 | Illumina HiSeq 2500 | 1 | |
EGAD00001002271 | Illumina HiSeq 2500 | 1 | |
EGAD00001002272 | Illumina HiSeq 2500 | 1 | |
EGAD00001002273 | Illumina HiSeq 2500 | 1 | |
EGAD00001002274 | Illumina HiSeq 2500 | 1 | |
EGAD00001002275 | Illumina HiSeq 2500 | 1 |