title: Homozygous p53 gene mutation in a radiation-induced glioblastoma 10 years after treatment for an intracranial germ cell tumor: case report.
abstract: 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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurosurgery, University of Hokkaido School of Medicine, Sapporo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tada
authors.forename: Y
authors.initials: Y
authors.lastname: Sawamura
authors.forename: H
authors.initials: H
authors.lastname: Abe
authors.forename: R
authors.initials: R
authors.lastname: Iggo
mesh_terms: D000293:Adolescent; D000483:Alleles; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D002872:Chromosome Deletion; D016371:Cranial Irradiation; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D005625:Frontal Lobe / Q000473:pathology; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006720:Homozygote; D006801:Humans; D009373:Neoplasms, Germ Cell and Embryonal / Q000532:radiotherapy; D009381:Neoplasms, Radiation-Induced / Q000235:genetics* / Q000473:pathology; D016609:Neoplasms, Second Primary / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53