Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Jul 31:4:e07420.
doi: 10.7554/eLife.07420.

Registered report: Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases

Brad Evans  1 , Erin Griner  2 ; Reproducibility Project: Cancer Biology
Collaborators, Affiliations

Registered report: Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases

Brad Evans et al. Elife. .

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 'Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases' by Xu and colleagues, published in Cancer Cell in 2011 (Xu et al., 2011). The key experiments being replicated include Supplemental Figure 3I, which demonstrates that transfection with mutant forms of IDH1 increases levels of 2-hydroxyglutarate (2-HG), Figures 3A and 8A, which demonstrate changes in histone methylation after treatment with 2-HG, and Figures 3D and 7B, which show that mutant IDH1 can effect the same changes as treatment with excess 2-HG. The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published by eLife.

Keywords: 2-hydroxyglutarate; IDH; Reproducibility Project: Cancer Biology; biochemistry; human; human biology; medicine; methodology.

PubMed Disclaimer

Conflict of interest statement

RP:CB: We disclose that EI, FT, and JL are employed by and hold shares in Science Exchange Inc. The experiments presented in this manuscript will be conducted by BE at the Proteomics and Mass Spectrometry Facility, which is a Science Exchange lab.

The other authors declare that no competing interests exist.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Akbay EA, Moslehi J, Christensen CL, Saha S, Tchaicha JH, Ramkissoon SH, Stewart KM, Carretero J, Kikuchi E, Zhang H, Cohoon TJ, Murray S, Liu W, Uno K, Fisch S, Jones K, Gurumurthy S, Gliser C, Choe S, Keenan M, Son J, Stanley I, Losman JA, Padera R, Bronson RT, Asara JM, Abdel-Wahab O, Amrein PC, Fathi AT, Danial NN, Kimmelman AC, Kung AL, Ligon KL, Yen KE, Kaelin WG, Bardeesy N, Wong KK. D-2-hydroxyglutarate produced by mutant IDH2 causes cardiomyopathy and neurodegeneration in mice. Genes & Development. 2014;28:479–490. doi: 10.1101/gad.231233.113. - DOI - PMC - PubMed
    1. Duncan CG, Barwick BG, Jin G, Rago C, Kapoor-Vazirani P, Powell DR, Chi JT, Bigner DD, Vertino PM, Yan H. A heterozygous IDH1R132H/WT mutation induces genome-wide alterations in DNA methylation. Genome Research. 2012;22:2339–2355. doi: 10.1101/gr.132738.111. - DOI - PMC - PubMed
    1. Errington TM, Iorns E, Gunn W, Tan FE, Lomax J, Nosek BA. An open investigation of the reproducibility of cancer biology research. Elife. 2014;3 doi: 10.7554/eLife.04333. - DOI - PMC - PubMed
    1. Faul F, Erdfelder E, Lang AG, Buchner A. G* Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behavior Research Methods. 2007;39:175–191. doi: 10.3758/BF03193146. - DOI - PubMed
    1. Figueroa ME, Abdel-Wahab O, Lu C, Ward PS, Patel J, Shih A, Li Y, Bhagwat N, Vasanthakumar A, Fernandez HF, Tallman MS, Sun Z, Wolniak K, Peeters JK, Liu W, Choe SE, Fantin VR, Paietta E, Löwenberg B, Licht JD, Godley LA, Delwel R, Valk PJM, Thompson CB, Levine RL, Melnick A. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell. 2010;18:553–567. doi: 10.1016/j.ccr.2010.11.015. - DOI - PMC - PubMed

Publication types

MeSH terms

Grants and funding

The Reproducibility Project: Cancer Biology is funded by the Laura and John Arnold Foundation, provided to the Center for Open Science in collaboration with Science Exchange. The funder had no role in study design or the decision to submit the work for publication.