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

eLife | 2018

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.

Pubmed ID: 29313488 RIS Download

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RRID:SCR_003238

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RRID:CVCL_0426

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View all literature mentions

SaOS-2 (cell line)

RRID:CVCL_0548

Cell line SaOS-2 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

StepOne Software (software resource)

RRID:SCR_014281

A software program for the Applied Biosystems StepOne and StepOnePlus Real-Time PCR Systems. StepOne software allows the user to open and analyze experiments generated from either the StepOne or the StepOnePlus system. Users can set up experiments, send experiments to the instrument, control the instrument settings, and collect and analyze data.

View all literature mentions

GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

View all literature mentions

ImageJ (software resource)

RRID:SCR_003070

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View all literature mentions

MES-SA (cell line)

RRID:CVCL_1404

Cell line MES-SA is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

DoTc2 4510 (cell line)

RRID:CVCL_1181

Cell line DoTc2 4510 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

G-292 clone A141B1 (cell line)

RRID:CVCL_2909

Cell line G-292 clone A141B1 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

SJSA-1 (cell line)

RRID:CVCL_1697

Cell line SJSA-1 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

U2OS (cell line)

RRID:CVCL_0042

Cell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

CHLA-10 (cell line)

RRID:CVCL_6583

Cell line CHLA-10 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

SK-N-MC (cell line)

RRID:CVCL_0530

Cell line SK-N-MC is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

TC-71 (cell line)

RRID:CVCL_2213

Cell line TC-71 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

A-673 (cell line)

RRID:CVCL_0080

Cell line A-673 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

Open Science Framework (storage service resource)

RRID:SCR_003238

Platform to support research and enable collaboration. Used to discover projects, data, materials, and collaborators helpful to your own research.

View all literature mentions

143B (cell line)

RRID:CVCL_2270

Cell line 143B is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HOS (cell line)

RRID:CVCL_0312

Cell line HOS is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

R Project for Statistical Computing (software resource)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

View all literature mentions

R Project for Statistical Computing (software resource)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

View all literature mentions

143B (cell line)

RRID:CVCL_2270

Cell line 143B is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HOS (cell line)

RRID:CVCL_0312

Cell line HOS is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

R Project for Statistical Computing (software resource)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

View all literature mentions

143B (cell line)

RRID:CVCL_2270

Cell line 143B is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HOS (cell line)

RRID:CVCL_0312

Cell line HOS is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions