Transcriptional signature of an adult brain tumor in <it>Drosophila</it>

• Main Authors: Loop Thomas, Leemans Ronny, Stiefel Urs, Hermida Leandro, Egger Boris, Xie Fukang, Primig Michael, Certa Ulrich, Fischbach Karl-Friedrich, Reichert Heinrich, Hirth Frank
• Format: Article
• Language: English
• Published: BMC 2004-04-01
• Series: BMC Genomics
• Online Access: http://www.biomedcentral.com/1471-2164/5/24

<p>Abstract</p> <p>Background</p> <p>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 <it>in vivo </it>transcriptional activity associated with a brain tumor, we carried out genome-wide microarray expression analyses of an adult brain tumor in <it>Drosophila </it>caused by homozygous mutation in the tumor suppressor gene <it>brain tumor (brat)</it>.</p> <p>Results</p> <p>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 <it>brat</it>^{<it>k06028 </it>}mutant brain tumor. Cross-validation and stringent statistical criteria identified a core transcriptional signature of <it>brat</it>^{<it>k06028 </it>}neoplastic tissue. We find significant expression level changes for 321 annotated genes associated with the adult neoplastic <it>brat</it>^{<it>k06028 </it>}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.</p> <p>Conclusion</p> <p>Our results identify for the first time the genome-wide transcriptional alterations associated with an adult brain tumor in <it>Drosophila </it>and reveal insights into the possible mechanisms of tumor formation caused by homozygous mutation of the translational repressor <it>brat</it>.</p>