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Molecular and phenotypic characterisation of paediatric glioma cell lines as models for preclinical drug development.
- Source :
-
PloS one [PLoS One] 2009; Vol. 4 (4), pp. e5209. Date of Electronic Publication: 2009 Apr 14. - Publication Year :
- 2009
-
Abstract
- Background: Although paediatric high grade gliomas resemble their adult counterparts in many ways, there appear to be distinct clinical and biological differences. One important factor hampering the development of new targeted therapies is the relative lack of cell lines derived from childhood glioma patients, as it is unclear whether the well-established adult lines commonly used are representative of the underlying molecular genetics of childhood tumours. We have carried out a detailed molecular and phenotypic characterisation of a series of paediatric high grade glioma cell lines in comparison to routinely used adult lines.<br />Principal Findings: All lines proliferate as adherent monolayers and express glial markers. Copy number profiling revealed complex genomes including amplification and deletions of genes known to be pivotal in core glioblastoma signalling pathways. Expression profiling identified 93 differentially expressed genes which were able to distinguish between the adult and paediatric high grade cell lines, including a number of kinases and co-ordinated sets of genes associated with DNA integrity and the immune response.<br />Significance: These data demonstrate that glioma cell lines derived from paediatric patients show key molecular differences to those from adults, some of which are well known, whilst others may provide novel targets for evaluation in primary tumours. We thus provide the rationale and demonstrate the practicability of using paediatric glioma cell lines for preclinical and mechanistic studies.
- Subjects :
- Adult
Astrocytes metabolism
Biomarkers metabolism
Child
Chromosome Aberrations
Enzyme Activation
Epigenesis, Genetic
Gene Expression Profiling
Humans
Immunophenotyping
Loss of Heterozygosity
Mitogen-Activated Protein Kinases metabolism
Phosphatidylinositol 3-Kinases metabolism
Signal Transduction physiology
Stem Cells metabolism
Cell Line, Tumor metabolism
Cell Line, Tumor pathology
Drug Design
Glioma genetics
Glioma metabolism
Glioma pathology
Phenotype
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 4
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 19365568
- Full Text :
- https://doi.org/10.1371/journal.pone.0005209