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Molecular and phenotypic characterisation of paediatric glioma cell lines as models for preclinical drug development.

Authors :
Bax DA
Little SE
Gaspar N
Perryman L
Marshall L
Viana-Pereira M
Jones TA
Williams RD
Grigoriadis A
Vassal G
Workman P
Sheer D
Reis RM
Pearson AD
Hargrave D
Jones C
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.

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