1: Generate omics data from six high-grade glioma stem cell cultures.
2: Computational modelling in search for new cancer driver genes and alterations.
3: Validate a subset of the findings in the six paediatric glioblastoma stem cell lines.
We have established six unique cancer stem cell cultures derived from paediatric glioblastoma tumour samples. As cancer stem cells are thought to be resistant to current treatment procedures in terms of chemo and radiation therapy and be a likely cause of relapse is an increased biological understanding of these cells of urgent need. We aim to perform detailed molecular profiling and identification of new possible drug targets with the help of these cell cultures.
1: RNA-seq for profiling of mRNA levels. Exome seq in search for point mutations will be performed on cell lines and their corresponding tumour and blood samples. ATAC-seq to measure chromatin accessibility will be performed on cell lines and tumour samples. Already available data include miRNA arrays and methylation arrays.
2: We will develop a computational model designed to search for associations between altered states of the genetic material with the expression of miRNAs and mRNAs, to find new cancer driver genes or alterations that are of significance in the paediatric brain cancer stem cells.
3. We will validate the most promising candidates in the cell lines, for example by knock-down, over-expression, and alteration of methylation or mutation state with the help of CRISPR.
As glioblastoma is one of the most severe brain tumours in children it is of high importance to identify new potential drug targets that can target the cancer stem cells. This is the first step towards developing new drugs that can prevent relapses and increase survival in affected children.