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

<h4>Background</h4>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 f...

Full description

Saved in:
Bibliographic Details
Main Authors: Dorine A Bax, Suzanne E Little, Nathalie Gaspar, Lara Perryman, Lynley Marshall, Marta Viana-Pereira, Tania A Jones, Richard D Williams, Anita Grigoriadis, Gilles Vassal, Paul Workman, Denise Sheer, Rui M Reis, Andrew D J Pearson, Darren Hargrave, Chris Jones
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0005209&type=printable
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850240375528095744
author Dorine A Bax
Suzanne E Little
Nathalie Gaspar
Lara Perryman
Lynley Marshall
Marta Viana-Pereira
Tania A Jones
Richard D Williams
Anita Grigoriadis
Gilles Vassal
Paul Workman
Denise Sheer
Rui M Reis
Andrew D J Pearson
Darren Hargrave
Chris Jones
author_facet Dorine A Bax
Suzanne E Little
Nathalie Gaspar
Lara Perryman
Lynley Marshall
Marta Viana-Pereira
Tania A Jones
Richard D Williams
Anita Grigoriadis
Gilles Vassal
Paul Workman
Denise Sheer
Rui M Reis
Andrew D J Pearson
Darren Hargrave
Chris Jones
author_sort Dorine A Bax
collection DOAJ
description <h4>Background</h4>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.<h4>Principal findings</h4>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.<h4>Significance</h4>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.
format Article
id doaj-art-4d6745336d244c4e8dc3df8b58736e76
institution OA Journals
issn 1932-6203
language English
publishDate 2009-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj-art-4d6745336d244c4e8dc3df8b58736e762025-08-20T02:00:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0144e520910.1371/journal.pone.0005209Molecular and phenotypic characterisation of paediatric glioma cell lines as models for preclinical drug development.Dorine A BaxSuzanne E LittleNathalie GasparLara PerrymanLynley MarshallMarta Viana-PereiraTania A JonesRichard D WilliamsAnita GrigoriadisGilles VassalPaul WorkmanDenise SheerRui M ReisAndrew D J PearsonDarren HargraveChris Jones<h4>Background</h4>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.<h4>Principal findings</h4>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.<h4>Significance</h4>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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0005209&type=printable
spellingShingle Dorine A Bax
Suzanne E Little
Nathalie Gaspar
Lara Perryman
Lynley Marshall
Marta Viana-Pereira
Tania A Jones
Richard D Williams
Anita Grigoriadis
Gilles Vassal
Paul Workman
Denise Sheer
Rui M Reis
Andrew D J Pearson
Darren Hargrave
Chris Jones
Molecular and phenotypic characterisation of paediatric glioma cell lines as models for preclinical drug development.
PLoS ONE
title Molecular and phenotypic characterisation of paediatric glioma cell lines as models for preclinical drug development.
title_full Molecular and phenotypic characterisation of paediatric glioma cell lines as models for preclinical drug development.
title_fullStr Molecular and phenotypic characterisation of paediatric glioma cell lines as models for preclinical drug development.
title_full_unstemmed Molecular and phenotypic characterisation of paediatric glioma cell lines as models for preclinical drug development.
title_short Molecular and phenotypic characterisation of paediatric glioma cell lines as models for preclinical drug development.
title_sort molecular and phenotypic characterisation of paediatric glioma cell lines as models for preclinical drug development
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0005209&type=printable
work_keys_str_mv AT dorineabax molecularandphenotypiccharacterisationofpaediatricgliomacelllinesasmodelsforpreclinicaldrugdevelopment
AT suzanneelittle molecularandphenotypiccharacterisationofpaediatricgliomacelllinesasmodelsforpreclinicaldrugdevelopment
AT nathaliegaspar molecularandphenotypiccharacterisationofpaediatricgliomacelllinesasmodelsforpreclinicaldrugdevelopment
AT laraperryman molecularandphenotypiccharacterisationofpaediatricgliomacelllinesasmodelsforpreclinicaldrugdevelopment
AT lynleymarshall molecularandphenotypiccharacterisationofpaediatricgliomacelllinesasmodelsforpreclinicaldrugdevelopment
AT martavianapereira molecularandphenotypiccharacterisationofpaediatricgliomacelllinesasmodelsforpreclinicaldrugdevelopment
AT taniaajones molecularandphenotypiccharacterisationofpaediatricgliomacelllinesasmodelsforpreclinicaldrugdevelopment
AT richarddwilliams molecularandphenotypiccharacterisationofpaediatricgliomacelllinesasmodelsforpreclinicaldrugdevelopment
AT anitagrigoriadis molecularandphenotypiccharacterisationofpaediatricgliomacelllinesasmodelsforpreclinicaldrugdevelopment
AT gillesvassal molecularandphenotypiccharacterisationofpaediatricgliomacelllinesasmodelsforpreclinicaldrugdevelopment
AT paulworkman molecularandphenotypiccharacterisationofpaediatricgliomacelllinesasmodelsforpreclinicaldrugdevelopment
AT denisesheer molecularandphenotypiccharacterisationofpaediatricgliomacelllinesasmodelsforpreclinicaldrugdevelopment
AT ruimreis molecularandphenotypiccharacterisationofpaediatricgliomacelllinesasmodelsforpreclinicaldrugdevelopment
AT andrewdjpearson molecularandphenotypiccharacterisationofpaediatricgliomacelllinesasmodelsforpreclinicaldrugdevelopment
AT darrenhargrave molecularandphenotypiccharacterisationofpaediatricgliomacelllinesasmodelsforpreclinicaldrugdevelopment
AT chrisjones molecularandphenotypiccharacterisationofpaediatricgliomacelllinesasmodelsforpreclinicaldrugdevelopment