Research article

Transcriptional signature of an adult brain tumor in Drosophila

Thomas Loop¹ , Ronny Leemans¹ , Urs Stiefel¹ , Leandro Hermida² , Boris Egger¹ , Fukang Xie¹ , Michael Primig² , Ulrich Certa³ , Karl-Friedrich Fischbach⁴ , Heinrich Reichert¹ and Frank Hirth¹

¹  Institute of Zoology, Biocenter/Pharmacenter, University of Basel, Klingelbergstr. 50, CH-4056 Basel, Switzerland

²  Biocenter, University of Basel, Klingelbergstr. 70, CH-4056 Basel, Switzerland

³  Roche Genetics Pharmaceuticals Division, F. Hoffmann-La Roche Ltd, CH-4070 Basel, Switzerland

⁴  Institute of Biology III, University of Freiburg, Schaenzlestrasse 1, D-79104 Freiburg, Germany

author email corresponding author email

BMC Genomics 2004, 5:24doi:10.1186/1471-2164-5-24

Published:	16 April 2004

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 brat^k06028 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.

Conclusion

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.