title: Relationships linking amplification level to gene over-expression in gliomas.
abstract: BACKGROUND
  Gene amplification is thought to promote over-expression of genes favouring tumour development. Because amplified regions are usually megabase-long, amplification often concerns numerous syntenic or non-syntenic genes, among which only a subset is over-expressed. The rationale for these differences remains poorly understood.
  
  
  RESULTS
  To address this question, we used quantitative RT-PCR to determine the expression level of a series of co-amplified genes in five xenografted and one fresh human gliomas. These gliomas were chosen because we have previously characterised in detail the genetic content of their amplicons. In all the cases, the amplified sequences lie on extra-chromosomal DNA molecules, as commonly observed in gliomas. We show here that genes transcribed in non-amplified gliomas are over-expressed when amplified, roughly in proportion to their copy number, while non-expressed genes remain inactive. When specific antibodies were available, we also compared protein expression in amplified and non-amplified tumours. We found that protein accumulation barely correlates with the level of mRNA expression in some of these tumours.
  
  
  CONCLUSIONS
  Here we show that the tissue-specific pattern of gene expression is maintained upon amplification in gliomas. Our study relies on a single type of tumour and a limited number of cases. However, it strongly suggests that, even when amplified, genes that are normally silent in a given cell type play no role in tumour progression. The loose relationships between mRNA level and protein accumulation and/or activity indicate that translational or post-translational events play a key role in fine-tuning the final outcome of amplification in gliomas.
authors.affiliation: Institut Curie, Centre de Recherche, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vogt
authors.forename: Anne
authors.initials: A
authors.lastname: Gibaud
authors.forename: Anna
authors.initials: A
authors.lastname: Almeida
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ourliac-Garnier
authors.forename: Michelle
authors.initials: M
authors.lastname: Debatisse
authors.forename: Bernard
authors.initials: B
authors.lastname: Malfoy
mesh_terms: D001932:Brain Neoplasms / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D018450:Disease Progression; D066246:ErbB Receptors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D005909:Glioblastoma / Q000378:metabolism; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D009368:Neoplasm Transplantation; D009837:Oligodendroglioma / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D004247:DNA; D066246:ErbB Receptors; D019098:Telomerase