title: Transcriptional signature of an adult brain tumor in Drosophila.
abstract: BACKGROUND
  Mutations and gene expression alterations in brain tumors have been extensively investigated, however the causes of brain tumorigenesis are largely unknown. Animal models are necessary to correlate altered transcriptional activity and tumor phenotype and to better understand how these alterations cause malignant growth. In order to gain insights into the in vivo transcriptional activity associated with a brain tumor, we carried out genome-wide microarray expression analyses of an adult brain tumor in Drosophila caused by homozygous mutation in the tumor suppressor gene brain tumor (brat).
  
  
  RESULTS
  Two independent genome-wide gene expression studies using two different oligonucleotide microarray platforms were used to compare the transcriptome of adult wildtype flies with mutants displaying the adult bratk06028 mutant brain tumor. Cross-validation and stringent statistical criteria identified a core transcriptional signature of brat(k06028) neoplastic tissue. We find significant expression level changes for 321 annotated genes associated with the adult neoplastic brat(k06028) tissue indicating elevated and aberrant metabolic and cell cycle activity, upregulation of the basal transcriptional machinery, as well as elevated and aberrant activity of ribosome synthesis and translation control. One fifth of these genes show homology to known mammalian genes involved in cancer formation.
  
  
  CONCLUSIONS
  Our results identify for the first time the genome-wide transcriptional alterations associated with an adult brain tumor in Drosophila and reveal insights into the possible mechanisms of tumor formation caused by homozygous mutation of the translational repressor brat.
authors.affiliation: Institute of Zoology, Biocenter/Pharmacenter, University of Basel, Klingelbergstr, 50, CH-4056 Basel, Switzerland. Frank.Hirth@unibas.ch
authors.forename: Thomas
authors.initials: T
authors.lastname: Loop
authors.forename: Ronny
authors.initials: R
authors.lastname: Leemans
authors.forename: Urs
authors.initials: U
authors.lastname: Stiefel
authors.forename: Leandro
authors.initials: L
authors.lastname: Hermida
authors.forename: Boris
authors.initials: B
authors.lastname: Egger
authors.forename: Fukang
authors.initials: F
authors.lastname: Xie
authors.forename: Michael
authors.initials: M
authors.lastname: Primig
authors.forename: Ulrich
authors.initials: U
authors.lastname: Certa
authors.forename: Karl-Friedrich
authors.initials: KF
authors.lastname: Fischbach
authors.forename: Heinrich
authors.initials: H
authors.lastname: Reichert
authors.forename: Frank
authors.initials: F
authors.lastname: Hirth
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics*; D004734:Energy Metabolism / Q000235:genetics; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D006720:Homozygote; D006801:Humans; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010641:Phenotype; D011485:Protein Binding / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D016601:RNA-Binding Proteins; C412783:brat protein, Drosophila