MPC-08 Molecular risk stratification using genome-wide DNA methylation data of standard-risk medulloblastomas treated with 18-Gy craniospinal irradiation

A novel risk stratification of medulloblastoma has been proposed based on retrospective data from patients undergoing standard treatment. However, it remains unclear whether the classification is applicable to patients receiving reduced-dose craniospinal irradiation (CSI). We performed molecular diagnosis and copy number analysis using methylation array on patients with standard-risk medulloblastoma treated with 18 Gy CSI at our institution. Nine tumor samples were available for analysis from seven patients who had a median age of 7.4 years at disease onset and a median observation period of 73 months. Three patients had recurrence, and another patient developed radiation-induced glioblastoma. From the three recurrent cases, one was molecularly diagnosed as SHH subtype with MYCN amplification; another case was a Group 4 tumor without favorable prognostic chromosomal aberrations, and the remaining patient experienced a very late relapse despite low-risk stratification. Of the recurrence-free cases, one was classified as WNT subtype, and another was a Group 4 tumor with chromosome 7 gain, and loss of chromosomes 8 and 11, both of which were associated with good prognosis. Methylation analysis also unveiled the fact that the recurrent tumor diagnosed as relapsing medulloblastoma by conventional diagnostic tools was in fact a radiation-induced glioblastoma. Our data suggested that the new risk stratification may be useful for cases treated with CSI reduced to 18 Gy. However, due to the presence of the late-relapsed case stratified to low risk, further investigations with a larger cohort should be required to confirm the data.