2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity

American Association for the Advancement of Science (AAAS) - Tập 9 Số 375 - 2017
Parker L. Sulkowski1,2, Christopher D. Corso2, Nathaniel D. Robinson2, Susan E. Scanlon3,2, Karin Purshouse2, Hanwen Bai1, Yanfeng Liu2, Ranjini K. Sundaram2, Denise C. Hegan2, Nathan R. Fons3,2, G. Breuer3,2, Yuanbin Song4, Ketu Mishra-Gorur5, Henk M. De Feyter6, Robin A. de Graaf6, Yulia V. Surovtseva7, Maureen Kachman8, Stephanie Halene4, Murat Günel1,5, Peter M. Glazer1,2, Ranjit S. Bindra3,2
1Department of Genetics, Yale University School of Medicine, New Haven, CT 06520 USA
2Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.
3Department of Experimental Pathology, Yale University School of Medicine, New Haven, CT 06520, USA.
4Section of Hematology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
5Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06520 USA
6Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06520, USA
7Yale Center for Molecular Discovery, West Haven, CT 06516, USA
8Michigan Regional Comprehensive Metabolomics Resource Core, National Institute of Environmental Health Sciences (NIEHS) Children’s Health Exposure Analysis Resource for Metabolomics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Tóm tắt

The oncometabolite 2-hydroxyglutarate renders IDH1/2 mutant cancer cells deficient in homologous recombination and confers vulnerability to synthetic lethal targeting with PARP inhibitors.

Từ khóa


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American Association for the Advancement of Science (AAAS)

Tập 9 Số 375

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