HOMOZYGOUS P53 GENE MUTATION IN A RADIATION-INDUCED GLIOBLASTOMA 10 YEARS AFTER TREATMENT FOR AN INTRACRANIAL GERM-CELL TUMOR - CASE-REPORT

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 i n the right frontal lobe 10 years after treatment of a suprasellar ger m cell tumor with 50 Cy of ionizing radiation. The glioblastoma was un detectable on a high-resolution magnetic resonance image obtained 3 mo nths before diagnosis. METHODS AND RESULTS: A p53 functional assay was used to examine the transcriptional competence of the p53 tumor suppr essor gene. This assay scores the content of mutant p53 alleles in tum or and blood samples quantitatively as a percentage of red yeast colon ies. The glioblastoma contained 95% mutant p53 alleles, whereas blood from the patient and her parents contained only normal background leve ls of red colonies. Sequencing revealed that the mutation in the tumor was a 3-base pair deletion affecting codons 238 and 239. Intragenic d eletion within the p53 deoxyribonucleic acid binding domain is uncommo n in sporadic tumors but would be entirely consistent with misrepair o f a radiation-induced double-strand deoxyribonucleic acid break in thi s case. CONCLUSION: This is the first case in which a causative underl ying genetic event has been identified in a radiation-induced glioblas toma. We infer that mutation of one p53 allele occurred at the time of radiotherapy, and the sudden appearance of the tumor 10 years later o ccurred after loss of the remaining wild-type allele and/or other gene tic alterations, such as chromosome 10 loss and epidermal growth facto r receptor gene amplification.