P07.01 Functional role of N-Myc in SHH type TP53 mutated MB’s metabolism

Abstract BACKGROUND Medulloblastoma is classified in 4 subgroups. Prognosis and therapeutic option was different from each subgroups. Thus, we need subgroup-specific in vitro models for investigating new therapeutic targets. Little established medulloblastoma cell-lines, which have been subgrouped is available. Especially, commercially available SHH type TP53 mutated cell-line is only DAOY. We established new cell lines 505CSC / 507FBS from the patient with SHH type with TP53 mutated MB. This matched pair cell line showed high expression of N-MYC in serum free conditioned medium. To know the functional role of N-MYC in MB, we used 507CSC and DAOY. MATERIAL AND METHODS Using chemical inhibitor of N-Myc in 507CSC and DAOY, proliferation assay, mRNA expression and measurements of ex-vivo metabolic phenotype were performed. RESULTS N-MYC inhibition leads to cell death in both cell lines. N-MYC regulated glucose, glutamine and methionine metabolism. Especially the targets were PKM2, GLS2, MAT2A, DNMT1 and 3A. CONCLUSION N-MYC is a target of therapy in a patient with SHH type TP53 mutated medulloblastoma.