ИСТИНА

Medulloblastoma, the most common CNS malignancy of childhood, is known for a significant clinical heterogeneity. The aim of the study was investigation of prognostic molecular-genetic biomarkers in Russian cohort of medulloblastoma patients. Molecular subgrouping was performed by gene expression profiling using Nanostring and copy number variation (CNV) analysis by MLPA in 50 primary FFPE tumor samples. All patients were treated according to HIT protocol. Median of follow-up time achieved 23.3 months. Molecular group distribution was as follows: WNT- 8, SHH- 14, group 3- 16, group 4- 27 patients. Different histological variants were present within all molecular subgroups with the exception of WNT where only classical variant was present. Separation of medulloblastoma into molecular subgroups had prognostic significance with event-free survival (EFS) for WNT- 1.00, SHH- 0.70(0.18), group3 – 0.40(0.14), group4- 0.76(0.11). In the whole cohort of patients only gain or amplification of 8q.24(MYC) had prognostication (EFS 0.17(0.14) vs. 0.70(0.07), p<0.001). None cytogenetic markers had prognostic significance in patients with WNT and SHH subgroups due to limited number of patients, while in group3 presence of gain6p (p=0.001), gain17q (p=0.017) and 10q deletion (p=0.021) led to dismal outcome. Also EFS in patients harboring gain of 8q24 (MYC) tended to decrease (p=0.081). Presence of isochromosome 17q had negative prognostic significance in group4 patients (p=0.023) while separate gain17q also had influence on EFS (p=0.086). Thus molecular subgrouping of medulloblastoma together with CNV data are clinically relevant and suitable to be prognostic biomarkers for patient’s stratification into risk groups.