MDB-16. CLINICAL AND MOLECULAR CHARACTERISTICS OF JAPANESE MEDULLOBLASTOMA, WNT-ACTIVATED

Abstract

Abstract BACKGROUND Medulloblastomas are at least classified into four core subgroups, including WNT-activated, SHH-activated, group 3 and group 4. These molecular subgroups have been introduced in the latest WHO classification, which has become fundamental and indispensable. Medulloblastoma, WNT-activated (WNT-MB) accounts for about 10% of all medulloblastomas, and their prognosis is excellent, and it is desired to ensure that patients with WNT-MBs are diagnosed exactly. In this study, we have summarized results of molecular analysis of Japanese MBs collected by Japanese Pediatric Molecular Neuro-oncology Group (JPMNG) study, and analyzed clinical and molecular characteristics of WNT-MBs. METHODS We enrolled 267 cases of medulloblastoma from 44 centers participating in the JPMNG study since 2012.Central histopathological diagnosis was performed by three neuropathologists, and molecular genetic diagnosis was performed using molecular subgrouping, DNA sequencing (CTNNB1), and copy number analysis. RESULTS A total of 244 cases were finally analyzed, and the 4-subgroup classification was WNT: 39 (16%), SHH: 61 (25%), group3: 42 (17%), and group4: 102 (41.8%), respectively. The age at diagnosis was 3 years or older (6-40 years) in all cases, with no cases occurring in infants, the majority being children (6-18 years) (31/39: 79.5%), and 8 cases (8/39: 20.5%) in adults older than 18 years. Histological features were classic (CMB) in the majority of cases and large cell (LCA) type in only 2 cases. The positivity rate of nuclear β-catenin by Immunological staining was 9 out of 12 (75%) of the cases examined. While, CTNNB1mutation was positive in 39 of 39 cases (100%) and monosomy 6 was also positive in 35 of 35 cases (100%), respectively. The 5-year survival rate was 91.9%. CONCLUSIONS Clinical characteristics of Japanese WBT-MB were almost similar to those reported in other countries, which showed excellent prognosis, and their molecular genetic status were also identical with results from other ethnics.