Using transgenic RNAi technology, we have screened over 4000 genes to identify targets to inhibit malignant growth caused by the loss of function of
lethal(3)malignant brain tumour
in
Drosophila in vivo
. We have identified 131 targets, which belong to a wide range of gene ontologies. Most of these target genes are not significantly overexpressed in mbt tumours hence showing that, rather counterintuitively, tumour-linked overexpression is not a good predictor of functional requirement. Moreover, we have found that most of the genes upregulated in mbt tumours remain overexpressed in tumour-suppressed double-mutant conditions, hence revealing that most of the tumour transcriptome signature is not necessarily correlated with malignant growth. One of the identified target genes is
meiotic W68
(
mei-W68
), the
Drosophila
orthologue of the human cancer/testis gene
Sporulation-specific protein 11
(
SPO11
), the enzyme that catalyses the formation of meiotic double-strand breaks. We show that
Drosophila mei-W68/SPO11
drives oncogenesis by causing DNA damage in a somatic tissue, hence providing the first instance in which a
SPO11
orthologue is unequivocally shown to have a pro-tumoural role. Altogether, the results from this screen point to the possibility of investigating the function of human cancer relevant genes in a tractable experimental model organism like
Drosophila.