Properties of putative drivers in ovarian cancer. (A) Gene silencing effects of 395 known cancer genes with available shRNA data in 102 cancer cell lines. The distributions of log2ratios of the shRNA concentrations in the final cell population and the initial DNA pool (log2ratioshRNA, see Methods) were compared between known cancer genes, oncogenes, tumour suppressors and the non-mutated genes using Wilcoxon test. Complete data are reported in Additional file 2, Table S8. (B) Gene silencing effects of the 40 putative drivers identified with our pipeline, seven tumour suppressors and eight oncogenes with available shRNA data in 25 ovarian cancer cell lines. The list of known tumour suppressors and oncogenes associated with ovarian cancer was derived from the Cancer Gene Census . Complete data are reported in Additional file 2, Table S9. (C) Confirming evidence of the effect of RNAi on three putative drivers. The block of RB1CC1 and KDM5B via RNAi leads to RB1 repression, with a consequent loss of the ability of RB1 to promote cell differentiation  and senescence , respectively. Interestingly, the Rb pathway is a known key player in ovarian cancer . Similarly, anti-PRKCQ siRNAs inactivate CASP8. As a consequence, the CASP8/BCL10/MALT1 complex cannot be formed, thus preventing the cells to enter apoptosis . (D) Effect of putative drivers on cell proliferation and survival. Reported are the links with pathways involved in gene proliferation of 19 out of 56 putative drivers mutated in 13 out of 23 tumour samples. The sample ID where the gene is mutated is provided together with the number of ovarian cancer cell lines over the total that displayed increased proliferation upon gene silencing, when available.
D'Antonio and Ciccarelli Genome Biology 2013 14:R52 doi:10.1186/gb-2013-14-5-r52