Research ArticleCancer

IDH1-R132H acts as a tumor suppressor in glioma via epigenetic up-regulation of the DNA damage response

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Science Translational Medicine  13 Feb 2019:
Vol. 11, Issue 479, eaaq1427
DOI: 10.1126/scitranslmed.aaq1427

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Linking glioma metabolism and DNA repair

Mutations in isocitrate dehydrogenase 1 (IDH1) are frequently found in gliomas and are associated with better outcomes. Núñez et al. discovered that, in addition to its roles in metabolism and epigenetics, mutant IDH1 also helps maintain genomic stability in tumors by enhancing the DNA damage response. This finding helps explain why patients with IDH1-mutant tumors have better survival despite their tumors being less sensitive to radiation than other gliomas. The authors also examined the mechanism for this phenomenon in mouse models and demonstrated that pharmacological inhibition of the DNA damage response sensitizes IDH1-mutant tumors to radiation, suggesting a potential direction for further therapeutic advances.

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