Tumor genotype dictates radiosensitization after Atm deletion in brainstem gliomas

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