Replication Study: Systematic identification of genomic markers of drug sensitivity in cancer cells.

Abstract

In 2016, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Vanden Heuvel et al., 2016), that described how we intended to replicate selected experiments from the paper 'Systematic identification of genomic markers of drug sensitivity in cancer cells' (Garnett et al., 2012). Here we report the results. We found Ewing's sarcoma cell lines, overall, were more sensitive to the PARP inhibitor olaparib than osteosarcoma cell lines; however, while the effect was in the same direction as the original study (Figure 4C; Garnett et al., 2012), it was not statistically significant. Further, mouse mesenchymal cells transformed with either the <i>EWS-FLI1</i> or <i>FUS-CHOP</i> rearrangement displayed similar sensitivities to olaparib, whereas the Ewing's sarcoma cell line SK-N-MC had increased olaparib sensitivity. In the original study, mouse mesenchymal cells transformed with the <i>EWS-FLI1</i> rearrangement and SK-N-MC cells were found to have similar sensitivities to olaparib, whereas mesenchymal cells transformed with the <i>FUS-CHOP</i> rearrangement displayed a reduced sensitivity to olaparib (Figure 4E; Garnett et al., 2012). We also studied another Ewing's sarcoma cell line, A673: A673 cells depleted of <i>EWS-FLI1</i> or a negative control both displayed similar sensitivities to olaparib, whereas the original study reported a decreased sensitivity to olaparib when <i>EWS-FLI1</i> was depleted (Figure 4F; Garnett et al., 2012). Differences between the original study and this replication attempt, such as the use of different sarcoma cell lines and level of knockdown efficiency, are factors that might have influenced the outcomes. Finally, where possible, we report meta-analyses for each result.