title: Astrocytoma derived short-term cell cultures retain molecular signatures characteristic of the tumour in situ.
abstract: The heterogeneity of tumours and uncertainties surrounding derived short-term cell cultures and established cell lines fundamentally challenge the research and understanding of tumour growth and development. When tumour cells are cultured, changes are inevitably induced due to the artificial growth conditions. Several recent studies have questioned how representative established cell lines or derived short-term cell cultures are of the tumour in situ. We have characterised gene expression changes induced by short-term culture in astrocytoma in order to determine whether derived short-term cell cultures are representative of the tumour in situ. In comparison to the majority of studies, paired biopsies and derived short-term cultures were investigated to reduce the effects of long-term culture and inter-tumour variability when comparing biopsies and derived cultures from tumours with the same histology from different individuals. We have used the Affymetrix GeneChip U133A to generate gene expression profiles of 6 paediatric pilocytic astrocytoma (PA) biopsies and derived short-term cell cultures and 3 adult glioblastoma multiforme (GBM) biopsies and derived short-term cultures. Significant differential gene expression is induced by short-term culture. However, when the biopsy and derived short-term cell culture samples were grouped according to tumour type (PA and GBM) a molecular signature of 608 genes showed significant differential expression between the groups. This gene cohort can distinguish PA and GBM tumours, regardless of the sample source, suggesting that astrocytoma derived short-term cultures do retain key aspects of the global tumour expression profile and are representative of the tumour in situ. Furthermore, these genes are involved in pathways and functions characteristic of adult GBM including VEGF signalling, hypoxia and TP53 signalling.
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, London, WC1N 3BG, UK. n.potter@ion.ucl.ac.uk
authors.forename: Nicola E
authors.initials: NE
authors.lastname: Potter
authors.forename: K
authors.initials: K
authors.lastname: Phipps
authors.forename: W
authors.initials: W
authors.lastname: Harkness
authors.forename: R
authors.initials: R
authors.lastname: Hayward
authors.forename: D
authors.initials: D
authors.lastname: Thompson
authors.forename: T S
authors.initials: TS
authors.lastname: Jacques
authors.forename: B
authors.initials: B
authors.lastname: Harding
authors.forename: D G T
authors.initials: DG
authors.lastname: Thomas
authors.forename: J
authors.initials: J
authors.lastname: Rees
authors.forename: J L
authors.initials: JL
authors.lastname: Darling
authors.forename: T J
authors.initials: TJ
authors.lastname: Warr
mesh_terms: D000328:Adult; D000818:Animals; D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D002648:Child; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor