Cancer-associated isocitrate dehydrogenase mutations induce mitochondrial DNA instability.

ABSTRACT: A major advance in understanding the progression and prognostic outcome of certain cancers, such as low-grade gliomas, acute myeloid leukaemia, and chondrosarcomas, has been the identification of early-occurring mutations in the NADP⁺-dependent isocitrate dehydrogenase genes IDH1 and IDH2 These mutations result in the production of the onco-metabolite D-2-hydroxyglutarate (2HG), thought to contribute to disease progression. To better understand the mechanisms of 2HG pathophysiology, we introduced the analogous glioma-associated mutations into the NADP⁺isocitrate dehydrogenase genes (IDP1, IDP2, IDP3) in Saccharomyces cerevisiae Intriguingly, expression of the mitochondrial IDP1^R148H mutant allele results in high levels of 2HG production as well as extensiv

SUBMITTER: Kingsbury JM 

PROVIDER: S-EPMC5179947 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature