Molecular subgrouping and characterization analysis of medulloblastomas in a cohort of Japanese patients

Abstract

Medulloblastoma is the most common solid malignancy and cause of oncologic death among children. Recent advances in genomic analysis obtained through international large-scale collaborations, Medulloblastoma Advanced Genomics International Consortium(MAGIC), have revealed that medulloblastomas can be classified into at least four distinct subgroups depending on their molecular expression profiles. These studies showed that the prognosis, age distributions, and molecular mechanisms of these subgroups of medulloblastomas completely differ from each other. Here we report the first analysis of molecular subgroups of medulloblastoma in Japanese patients(Shizuoka cohort). Molecular subgroups were predicted for 18 medulloblastomas;and age distributions, radiographic features, and histological characteristics were analyzed. It was predicted that 11% of the medulloblastomas were of the WNT type, 50% of the SHH type, 6% of the group 3 type, and 33% of the group 4 type. The percentage of group 3 type medulloblastomas was smaller than in the MAGIC study, while the percentage of the SHH type was larger. However, age distribution, recurrence-free survival, and overall survival for each group were quite similar to the MAGIC study. In addition, in an imaging study, 78% of patients with medulloblastomas of the SHH type presented tumors in the cerebellar hemispheres. The classical pathohistological hallmarks that may predict medulloblastoma prognosis were mainly seen in tumors of the SHH type. Molecular subgrouping of medulloblastomas could be important in the future, not only for prediction of prognosis, but also for decision making regarding the use of future new treatments such as molecular targeting therapy. The establishment of a public molecular analysis system of medulloblastomas in Japan is greatly desired, and it is currently under development;this database will help establish the molecular diagnosis of medulloblastomas in Japan.