Study

Comparison of EGF and PDGF driven glioblastomas.

Study ID Alternative Stable ID Type
EGAS00001001900 Other

Study Description

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 ... (Show More)

Study Datasets 7 datasets.

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Dataset ID Description Technology Samples
EGAD00001002269
We expressed PDGFRAmut, wild-type PDGFRA and a GFP control from lentivirus, in two primary GBM patient-derived cell lines that we had cultured as monolayers.
Illumina HiSeq 4000 1
EGAD00001002270
We collected fresh tissue from an untreated GBM (SF10282) directly from the operating room and subjected the biopsy to single-cell RNA-seq with the fluidigm C1 machine, resulting in sequencing libraries from 96 individual cells.
Illumina HiSeq 2500 1
EGAD00001002271
We collected fresh tissue from an untreated GBM (SF10345) directly from the operating room and subjected the biopsy to single-cell RNA-seq with the fluidigm C1 machine, resulting in sequencing libraries from 96 individual cells.
Illumina HiSeq 2500 1
EGAD00001002272
We collected fresh tissue from an untreated GBM (SF10360) directly from the operating room and subjected the biopsy to single-cell RNA-seq with the fluidigm C1 machine, resulting in sequencing libraries from 96 individual cells.
Illumina HiSeq 2500 1
EGAD00001002273
We performed bulk exome-seq on a primary GBM and a blood sample from SF10345
Illumina HiSeq 2500 1
EGAD00001002274
We performed bulk exome-seq on a primary GBM and a blood sample from SF10360
Illumina HiSeq 2500 1
EGAD00001002275
We performed bulk exome-seq on a primary GBM and a blood sample from SF10282
Illumina HiSeq 2500 1

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