Expression of GNAS, TP53, and PTEN Improves the Patient Prognostication in Sonic Hedgehog (SHH) Medulloblastoma...

Medulloblastoma (MB) is the most common malignant brain tumor in children. It is currently classified in four main molecular subgroups with different clinical outcomes: sonic hedgehog, wingless, group 3, and group 4 (MB_SHH, MB_WNT, MB_GRP3, or MB_GRP4). Presently, a 22-gene expression panel has been efficiently applied for molecular subgrouping using nCounter technology. In this study, formalin-fixed, paraffin-embedded samples from 164 Brazilian medulloblastomas were evaluated, applying the 22-gene panel, and subclassified into the low and high expression of nine key medulloblastoma-related genes. In addition, TP53 mutation status was assessed using TruSight Tumor 15 Panel, and its correlation with expression and prognostic impact was evaluated. Samples from 149 of 164 patients (90%) were classified into MB_SHH (47.7%), MB_WNT (16.1%), MB_GRP3 (15.4%), and MB_GRP4 (20.8%). GNAS presented the highest expression levels, with higher expression in MB_SHH. TP53, MYCN, SOX2, and MET were also up-regulated in MB_SHH, whereas PTEN was up-regulated in MB_GRP4. GNAS, TP53, and PTEN low expression was associated with the unfavorable patient outcome only for MB_SHH (P = 0.04, P = 0.01, and P = 0.02, respectively). TP53 mutations were detected in 28.57% of MB_SHH cases and exhibited association with lower expression and worse clinical outcome, although not statistically significant. The 22-gene panel for molecular classification of medulloblastoma associated with the expression of GNAS, TP53, and PTEN improves the patient prognostication in MB_SHH subgroup and can be easily incorporated in the 22-gene panel without any additional costs.