LAUSR

Abstract OBJECTIVE To determine the prognostic significance of the four molecular subgroups of medulloblastoma (MB) among children in Malaysia. METHODS We assembled MB samples of children < 18 years between January 1999 and July 2017 in University Malaya Medical Centre, Penang General Hospital, Sarawak General Hospital and Sabah Woman and Children’s Hospital. MB was sub-grouped using 850k DNA methylation profiling. RESULTS Fifty-one tumour samples were retrieved. Histopathological subtypes were classic (n=12), MB extensive nodularity/desmoplastic (n=9) and 30 MB results without subtypes. Thirteen patients were M1-M4. Fourteen patients were stratified as standard-risk (SR,27.4%), 22 as high-risk (HR,43.2%) and 15 as high-risk children ≤ 3 years old (iHR,29.4%). Molecular subgrouping revealed 16 Group4, 11 SHH, 10 Group3 and 4 Wnt. In 8 patients, DNA methylation profiling identified a diagnosis other than MB and in 2 samples the DNA was inadequate. For patients >3 years old, the 5-year event-free survival (EFS) was 35.7%±13% in HR and 39.7%±20% in SR. The 5-year overall survival (OS) in these two groups was 43.4%±14% and 41.7±30% respectively. iHR had 5-year EFS and OS of 48.0%±16% and 60.0%±16% respectively. WNT tumours had the best 5y-OS of 66.7±22% of the cohort, albeit significantly lower than other reports, followed by SHH (56.8±17%), Group4 (44.3±17.6%) and Group3 (41.7±18%). Treatment abandonment rate was 20%. CONCLUSION The discrepancy in the histological diagnoses highlights the importance of DNA methylation profiling technique for accurate diagnosis. We observed poor OS across all the subgroups, in part due to treatment abandonment.