TP53 and brain neoplasm: While the entire genome of the patient wasn't sequenced, making it difficult to pinpoint the timing of mutations, it's plausible that the patient's mutant PNKP-induced impairment in DNA replication occurred early on and, in combination with known pediatric glioma-associated mutations like ATRX and TP53 (71), contributed to the initiation and progression of the brain tumor.