## Registered report: IDH mutation impairs histone demethylation and results in a block to cell differentiation <br> **Abstract:** The [Reproducibility Project: Cancer Biology][1] seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of [citations and Altmetric scores][2] ([Errington et al., 2014][3]). This Registered Report describes the proposed replication plan of key experiments from “IDH mutation impairs histone demethylation and results in a block to cell differentiation” by Lu and colleagues, published in *Nature* in 2012 ([Lu et al., 2012][4]). The experiments that will be replicated are those reported in Figures 1B, 2A, 2B, 2D and 4D. Lu and colleagues demonstrated that expression of mutant forms of IDH1 or IDH2 caused global increases in histone methylation and increased levels of 2 hydroxyglutarate (Figure 1B). This was correlated with a block in differentiation (Figures 2A, B and D). This effect appeared to be mediated by the histone demethylase KDM4C (Figure 4D). The Reproducibility Project: Cancer Biology is a collaboration between the [Center for Open Science][5] and [Science Exchange][6], and the results of the replications will be published by [*eLife*][7]. ---------- ### Contents This component contains additional materials relating to the Registered Report for Study 47: Lu et al. 2012, Nature. The Registered Report can be found [here][8]. ---------- **Registered Report Initial Draft**: - This document represents the first draft of the selected experimental protocols. It contains the information that the Core team, with help from scientist volunteers, was able to glean from the original publication and its supplemental materials before the original authors were contacted for their input. - [Study 47 Registered Report Initial Draft][9] **Data Estimation**: - When original data was unable to be obtained, or original qualitative data was quantified (for example, Western blots), the estimated data is contained here. Examples include densitometric quantification of Western blot bands, or estimations of means and variances from published graphs. - [Study 47 Supp Fig 1A data estimation.pptx][10] - [Study 47 Supplemental Figure 8B data estimation.pptx][11] - [Study 47 Figure 2A 2HG.pptx][12] **Power Calculations**: - These documents contain details about how power calculations were performed, and include spreadsheets documenting statistical tests as well as any PRISM files, R scripts or additional materials used. - [Study 47 power calculations][13] - [Study 47 Supp Figure 1A 2-way ANOVA.R][14] - [Study 47 Figure 1B ANOVA.R][15] - [Screen shot of 2% RSD Figure 1B][16] - [Study 47 Figure 2A ANOVA.R][17] - [Screen shot of 2% RSD Figure 2A][18] - [Study 47 Figure 2D ANOVA.R][19] - [Study 47 Figure 4D and SF8A ANOVA.R][20] - [Screen shot of 2% RSD Figure 4D S8A H3K9me3][21] - [Screen shot of 2% RSD Figure 4D S8A KDM4C][22] - [Study 47 Supp Figure 8B ANOVA.R][23] [1]: https://osf.io/e81xl/wiki/home/ [2]: https://osf.io/e81xl/wiki/studies/ [3]: https://doi.org/10.7554/eLife.04333 [4]: https://doi.org/10.1038/nature10860 [5]: https://cos.io/ [6]: https://www.scienceexchange.com/ [7]: https://elifesciences.org/ [8]: https://elifesciences.org/articles/10860 [9]: https://osf.io/6w4d3/ [10]: https://osf.io/nmcxt/ [11]: https://osf.io/f4b3a/ [12]: https://osf.io/3z8qh/ [13]: https://osf.io/2q5sb/ [14]: https://osf.io/afkvg/ [15]: https://osf.io/mbc2j/ [16]: https://osf.io/cn4ty/ [17]: https://osf.io/kz8cf/ [18]: https://osf.io/qpv2t/ [19]: https://osf.io/3s4vp/ [20]: https://osf.io/3ufsx/ [21]: https://osf.io/f93by/ [22]: https://osf.io/nmp69/ [23]: https://osf.io/24zgm/