Abstract B018: Breaking down cancer: IDH and its impact on metabolism and DNA damage and repair

Metabolic reprogramming has been detected in many diseases, including cancer. Recently, a small number of metabolic enzymes have been identified as driver mutations for various types of cancer. To better understand how these genes lead to cancer, and to identify molecular targets for treatment, we are investigating the isocitrate dehydrogenase (IDH) mutation implicated in human glioma and acute myeloid leukemia. We are currently using Drosophila melanogaster as a model to study both the metabolic changes that occur when IDH is mutated, and the potential impact on DNA damage repair pathways. To analyze metabolic changes in the brain of IDH mutant flies, we have optimized a protocol for measuring the metabolism of whole brains using the XFe96 metabolic analyzer. We have also detected the expression of D2-HG, a metabolite produced by mutant IDH in human cells, in our fly IDH model. Generation of D2-HG in human cells has been reported to correlate with insufficient DNA repair. To study this further we are testing for increased DNA damage and lack of DNA repair initiation. In particular, we are investigating a hypothesized connection between the Fanconi anemia DNA repair pathway and IDH mutations. Citation Format: Kathryn Neville, Elizabeth Arcand, Gabriela Chiaramida, Kaylie O9Connell, Marla Tipping. Breaking down cancer: IDH and its impact on metabolism and DNA damage and repair [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B018.