Repository logo
 

Transcriptional signature of an adult brain tumor in Drosophila.


Change log

Authors

Loop, Thomas 
Leemans, Ronny 
Stiefel, Urs 
Hermida, Leandro 
Egger, Boris 

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. 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.

Description

Keywords

Animals, Apoptosis, Brain Neoplasms, Carrier Proteins, Cell Cycle, DNA Repair, DNA Replication, DNA-Binding Proteins, Drosophila, Drosophila Proteins, Energy Metabolism, Gene Expression Profiling, Genes, Tumor Suppressor, Homozygote, Humans, Mutation, Oligonucleotide Array Sequence Analysis, Phenotype, Protein Binding, Protein Biosynthesis, RNA-Binding Proteins, Signal Transduction, Transcription, Genetic

Journal Title

BMC Genomics

Conference Name

Journal ISSN

1471-2164
1471-2164

Volume Title

Publisher

Springer Science and Business Media LLC