Tumor genotype dictates radiosensitization after Atm deletion in primary brainstem glioma models

Diffuse intrinsic pontine glioma (DIPG) kills more children than any other type of brain tumor. Despite clinical trials testing many chemotherapeutic agents, palliative radiotherapy remains the standard treatment. Here, we utilized Cre/loxP technology to show that deleting Ataxia telangiectasia mutated (Atm) in primary mouse models DIPG can enhance tumor radiosensitivity. Genetic deletion Atm improved survival mice with p53-deficient but not p53 wild-type gliomas after radiotherapy. Similar patients DIPG, tumors had independent deletion. Primary cell lines induced proapoptotic genes radiation and repressed NRF2 target, NAD(P)H quinone dehydrogenase 1 (Nqo1). Tumors lacking Ink4a/Arf expressed highest level Nqo1 were most resistant radiation, enhanced response. These results suggest genotype may determine whether inhibition ATM during will be an effective approach treat DIPGs.