Supplemental Figures and figure legends 1 to 6 from An <i>in vivo</i> genetic screen in <i>Drosophila</i> identifies the orthologue of human cancer/testis gene <i>SPO11</i> among a network of targets to inhibit <i>lethal(3)malignant brain tumour</i> growth Fabrizio Rossi Cristina Molnar Kazuya Hashiyama Jan P. Heinen Judit Pampalona Salud Llamazares José Reina Tomomi Hashiyama Madhulika Rai Giulia Pollarolo Ismael Fernandez Cayetano Gonzalez 10.6084/m9.figshare.5306797.v1 https://rs.figshare.com/articles/journal_contribution/Supplemental_Figures_and_figure_legends_1_to_6_from_An_i_in_vivo_i_genetic_screen_in_i_Drosophila_i_identifies_the_orthologue_of_human_cancer_testis_gene_i_SPO11_i_among_a_network_of_targets_to_inhibit_i_lethal_3_malignant_brain_tumour_i_growth/5306797 Using transgenic RNAi technology, we have screened over 4.000 genes to identify targets to inhibit malignant growth caused by the loss of function of <i>lethal(3)malignant brain tumour</i> (mbt) in <i>Drosophila in vivo</i>. 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 <i>meiotic W68</i> (<i>mei-W68</i>), the <i>Drosophila</i> orthologue of the human Cancer Testes gene <i>Sporulation-specific protein 11</i> (<i>SPO11</i>), the enzyme that catalyses the formation of meiotic double-strand breaks. We show that <i>Drosophila mei-W68/SPO11</i> drives oncogenesis by causing DNA damage in a somatic tissue, hence providing the first instance in which a <i>SPO11</i> 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 <i>Drosophila.</i> 2017-08-14 08:59:54 l(3)mbt Drosophila malignant growth cancer testis antigens