MB-90: IDENTIFICATION OF ANDROGEN RECEPTOR MUTATIONS IN PEDIATRIC MEDULLOBLASTOMA

Medulloblastomas subtypes are now defined by molecular characteristics. Genetic analysis of a patient with Medulloblastoma (MB) revealed no mutations in known oncogenic drivers; however, her tumor had a mutation in the androgen receptor (AR). Mutations of AR have been characterized in other cancers, however, little is known about the role of androgen signaling in medulloblastoma. Analysis of a subset of MB showed that 20% of these tumors (n = 32) had mutations in genes associated with the AR pathway. The effects of these mutations on oncogenesis and prognosis are not known. To further investigate the potential effects of AR pathways in MB, expression analysis of hormone receptor pathway gene was run. Expression data were compared for mean equality via ANOVA model base on tumor subtype. No significant differences in the AR expression were noted. Expression of five related nuclear receptor pathway transcripts were statistically different between the subgroups. The genes related to AR functioning that were found to have differential expression between the various subtypes were DHCR24, FHL2, PIAS2, RHOA and TGFB1. DHCR24 is active in the biosynthesis of cholesterol and had significantly lower expression in Group 4. Group 4 tumors also demonstrated a decreased expression in RHOA which functions in cell migration and stabilization. The PIAS2 gene enhances the sumoylation of the AR and expression was decreased in Group 3. Understanding the effects of AR mutations and other related genes in the AR pathway in patients with medulloblastoma may provide information about a novel pathway involved in tumorigenesis and growth.