PATH-25. GENOME-WIDE METHYLATION ANALYSIS CAN SEGREGATE RADIATION-INDUCED GLIOBLASTOMA FROM LATE RECURRENCE OF MEDULLOBLATOMAS

Abstract It could be difficult to diagnose recurrent medulloblastoma with conventional diagnostic tools because other lesions mimic relapse of the tumor from both a morphological and radiological standpoint, particularly when it happens late. We report two medulloblastoma cases, both of which seemed to develop late-recurrence more than 5 years from the initial surgery. Genome-wide methylation analysis revealed that one of the recurrent tumors was in fact a radiation-induced glioblastoma. The first patient was a 6-year-old female patient who developed a posterior fossa tumor. The pathological diagnosis was medulloblastoma with focal desmoplasia. She was in complete remission for 9 years after the treatment but developed an intradural lesion in her thoracic spine. The lesion was biopsied and pathologically confirmed as recurrence of the tumor. The second patient was a female patient who developed non-metastatic medulloblastoma at the age of 10. She suffered local recurrence 5 years after the diagnosis. Biopsy was performed, and the pathological diagnosis was relapse of the tumor. We performed unsupervised hierarchical clustering of the methylation data from our cases and reference data. In contrast to consistency of methylation profiling and copy number abnormalities between primary and recurrent tumors of case 1, the analysis revealed that the recurrent tumor of case 2 was distinct from medulloblastomas and clustered with “IDH-wild type glioblastomas”, which suggested that the recurrent tumor was radiation-induced glioblastoma. This report highlights the clinical utility of molecular genetic/epigenetic approach to confirm diagnosis of brain tumor recurrence.