Objective: Radiation-induced glioma is a rare but serious complication of radiotherapy. Underlying radiation-induced mutations in oncogenes or tumor suppressor genes have not previously been described.
Clinical presentation: A 16-year-old female patient developed a glioblastoma in the right frontal lobe 10 years after treatment of a suprasellar germ cell tumor with 50 Gy ionizing radiation. The glioblastoma was undetectable on a high-resolution magnetic resonance image obtained 3 months before diagnosis.
Methods and results: A p53 functional assay was used to examine the transcriptional competence of the p53 tumor suppressor gene. This assay scores the content of mutant p53 alleles in tumor and blood samples quantitatively as a percentage of red yeast colonies. The glioblastoma contained 95% mutant p53 alleles, whereas blood from the patient and her parents contained only normal background levels of red colonies. Sequencing revealed that the mutation in the tumor was a 3-base pair deletion affecting codons 238 and 239. Intragenic deletion within the p53 deoxyribonucleic acid binding domain is uncommon in sporadic tumors but would be entirely consistent with misrepair of a radiation-induced double-strand deoxyribonucleic acid break in this case.
Conclusion: This is the first case in which a causative underlying genetic event has been identified in a radiation-induced glioblastoma. We infer that mutation of one p53 allele occurred at the time of radiotherapy, and the sudden appearance of the tumor 10 years later occurred after loss of the remaining wild-type allele and/or other genetic alterations, such as chromosome 10 loss and epidermal growth factor receptor gene amplification.