Objective
Glioblastoma multiforme (GBM) is the most malignant type of brain tumor in adults with a median survival of one year. The hallmarks of GBM are invasion and neo-angiogenesis. Recently, gene expression studies have established that overexpression of a “mesenchymal” gene signature co-segregate with the poor-prognosis group of glioma patients. We have revealed that two transcription factors, Stat3 and C/EBPβ behave as master regulators of the mesenchymal gene signature. Overexpression of these two transcription factors reprograms neural stem cells along the aberrant mesenchymal lineage, whereas gene silencing in glioma cancer initiating cells (CSC) reduce tumor growth and aggressiveness. Recently, the Cancer Genome Atlas Network has provided information on genomic abnormalities that have allowed the expansion of previous glioblastoma classification studies by associating known subtypes with specific genomic alterations. In particular, EGFR amplification and NF1 and PTEN loss have been linked with the mesenchymal tumor subtype. In this proposal, we would like to identify the genetic events that cause the aberrant expression of Stat3 and C/EBPβ and mesenchymal transformation of gliomas. We have hypothesized that this might occurs by (1) gene copy number variation, (2) mutation in the gene promoter, (3) gene mutation of an upstream transcriptional regulator or, alternatively (4) aberrant DNA methylation of the gene promoter. Will analyze Stat3 and C/EBPβ gene promoter as well as the gene status in GBM samples by performing copy number variation studies and promoter sequencing. The status of CpG methylation at the promoter will be evaluated by pyrosequencing. Finally, we will test the effect of EGFR amplification, as well as of NF1 and PTEN deletion. We will mimic gene deletion or amplification by silencing or overexpressing these genes in glioma CSC and evaluating the effects on cell invasion and tumor formation, both in vitro and in vivo.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics DNA
- medical and health sciences medical biotechnology cells technologies stem cells
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics genomes
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2010-RG
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
79106 Freiburg
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.