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

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...

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Autores principales: Vanden Heuvel, John P, Maddox, Ewa, Maalouf, Samar W
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760202/
https://www.ncbi.nlm.nih.gov/pubmed/29313488
http://dx.doi.org/10.7554/eLife.29747
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author Vanden Heuvel, John P
Maddox, Ewa
Maalouf, Samar W
author_facet Vanden Heuvel, John P
Maddox, Ewa
Maalouf, Samar W
author_sort Vanden Heuvel, John P
collection PubMed
description 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 EWS-FLI1 or FUS-CHOP 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 EWS-FLI1 rearrangement and SK-N-MC cells were found to have similar sensitivities to olaparib, whereas mesenchymal cells transformed with the FUS-CHOP 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 EWS-FLI1 or a negative control both displayed similar sensitivities to olaparib, whereas the original study reported a decreased sensitivity to olaparib when EWS-FLI1 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.
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spelling pubmed-57602022018-01-10 Replication Study: Systematic identification of genomic markers of drug sensitivity in cancer cells Vanden Heuvel, John P Maddox, Ewa Maalouf, Samar W eLife Cancer Biology 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 EWS-FLI1 or FUS-CHOP 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 EWS-FLI1 rearrangement and SK-N-MC cells were found to have similar sensitivities to olaparib, whereas mesenchymal cells transformed with the FUS-CHOP 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 EWS-FLI1 or a negative control both displayed similar sensitivities to olaparib, whereas the original study reported a decreased sensitivity to olaparib when EWS-FLI1 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. eLife Sciences Publications, Ltd 2018-01-09 /pmc/articles/PMC5760202/ /pubmed/29313488 http://dx.doi.org/10.7554/eLife.29747 Text en © 2017, Vanden Heuvel et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cancer Biology
Vanden Heuvel, John P
Maddox, Ewa
Maalouf, Samar W
Replication Study: Systematic identification of genomic markers of drug sensitivity in cancer cells
title Replication Study: Systematic identification of genomic markers of drug sensitivity in cancer cells
title_full Replication Study: Systematic identification of genomic markers of drug sensitivity in cancer cells
title_fullStr Replication Study: Systematic identification of genomic markers of drug sensitivity in cancer cells
title_full_unstemmed Replication Study: Systematic identification of genomic markers of drug sensitivity in cancer cells
title_short Replication Study: Systematic identification of genomic markers of drug sensitivity in cancer cells
title_sort replication study: systematic identification of genomic markers of drug sensitivity in cancer cells
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760202/
https://www.ncbi.nlm.nih.gov/pubmed/29313488
http://dx.doi.org/10.7554/eLife.29747
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