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


RESULTS
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.


CONCLUSIONS
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.
Bax
Dorine A
DA
Paediatric Oncology, The Institute of Cancer Research, Sutton, United Kingdom.
Little
Suzanne E
SE
Gaspar
Nathalie
N
Perryman
Lara
L
Marshall
Lynley
L
Viana-Pereira
Marta
M
Jones
Tania A
TA
Williams
Richard D
RD
Grigoriadis
Anita
A
Vassal
Gilles
G
Workman
Paul
P
Sheer
Denise
D
Reis
Rui M
RM
Pearson
Andrew D J
AD
Hargrave
Darren
D
Jones
Chris
C
D000328:Adult; D001253:Astrocytes / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D045744:Cell Line, Tumor / Q000378:metabolism / Q000473:pathology; D002648:Child; D002869:Chromosome Aberrations; D015195:Drug Design; D004789:Enzyme Activation; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D019656:Loss of Heterozygosity; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000378:metabolism
D015415:Biomarkers; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases