EP-02MOLECULAR CLASSIFICATION OF EPENDYMOMAS IN A JAPANESE COHORT

INTRODUCTION: Based on a series of extensive molecular analysis in the recent years, a scheme of molecular classification for ependymomas has been proposed. The efficacy of the classification however needs to be validated in an independent cohort of different ethnicity. For this purpose, Japan Pediatric Molecular Neuro-Oncology Group (JPMNG) has been established as a joint project of Japan Society of Neuro-Oncology (JSNO) and Japan Society of Pediatric Neurosurgery (JSPN) in order to centrally collect tumor samples and patient information and to provide a standardized molecular classification in pediatric brain tumors. METHODS: We studied genome-wide methylation analysis in ependymomas by using Infinium HumanMethylation450K BeadChip (HM450K). To detect C11orf95-RELA fusions and YAP1 associated fusions, we performed FISH and RT-PCR followed by Sanger sequencing,. Array CGH was used to assess chromothripsis in the cases with RELA or YAP1 fusions. RESULTS: The number of samples collected so far is 96. Among them, 64 samples (fresh frozen 53, FFPE 11) were analyzed with HM450K array. Posterior fossa (PF) ependymomas were subdivided into two groaups. One group, which clusters with reported PFA tumors, included all infantile-onset cases and histopathologically most anaplastic ependymoma (WHO grade3). The other includes most adult cases, ependymoma (WHO grade2) cases, and all primary spinal tumor cases and clustered with the PFB tumors. Supratentorial (ST) ependymomas had generally higher levels of methylation than either PFA or PFB tumors. C11orf95-RELA fusion gene were detected in 7 of 11 ST tumors. There were no C11orf95-YAP1 fusion positive cases examined by RT-PCR. Chromothripsis was detected in 2 out of 6 fusion-positive tumors. CONCLUSIONS: Japanese PF ependymomas were successfully classified into PFA and PFB by methylation profiling. C11orf95-RELA fusions were only observed in ST ependymomas but they may not be always associated with chromothripsis detected by array CGH. The pathogenesis of fusion-negative ST ependymomas needs further investigation.