title: Registered report: IDH mutation impairs histone demethylation and results in a block to cell differentiation.
abstract: The Reproducibility Project: Cancer Biology 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 (Errington et al., 2014). 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). 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 Scienceand Science Exchange, and the results of the replications will be published by eLife.
authors.affiliation: Cancer Metabolism Facility, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, United States.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Richarson
authors.affiliation: Cancer Metabolism Facility, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Scott
authors.affiliation: Cancer Metabolism Facility, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, United States.
authors.forename: Olga
authors.initials: O
authors.lastname: Zagnitko
authors.affiliation: Functional Genomics Core, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, United States.
authors.forename: Pedro
authors.initials: P
authors.lastname: Aza-Blanc
authors.affiliation: Functional Genomics Core, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, United States.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Washington University School of Medicine, St Louis, United States.
authors.forename: David A
authors.identifier: http://orcid.org/0000-0003-1009-2247
authors.initials: DA
authors.lastname: Russler-Germain
mesh_terms: D002454:Cell Differentiation; D002460:Cell Line; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D006657:Histones; D050505:Mutant Proteins; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
keywords: 2HG metabolism; IDH mutation; human; human biology; medicine; methodology; reproducibility project: cancer biology