Transcriptional signature of an adult brain tumor in Drosophila.
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.
Loop
Thomas
T
Institute of Zoology, Biocenter/Pharmacenter, University of Basel, Klingelbergstr, 50, CH-4056 Basel, Switzerland. Frank.Hirth@unibas.ch
Leemans
Ronny
R
Stiefel
Urs
U
Hermida
Leandro
L
Egger
Boris
B
Xie
Fukang
F
Primig
Michael
M
Certa
Ulrich
U
Fischbach
Karl-Friedrich
KF
Reichert
Heinrich
H
Hirth
Frank
F
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
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D016601:RNA-Binding Proteins; C412783:brat protein, Drosophila