In addition, like other alterations triggering DNA reparation, these mutations may participated in the activation of specific immunogenic pathways.38 These early PRKDC alterations may participate in the oncogenesis through increased DNA damage35 in the gradual increase of mutations seen in CMMRD glioma before the onset of the POLE/POLD1 mutation. The gene discussed is PRKDC; the disease is central nervous system cancer.