CBMS-10 FUNCTIONAL ROLE OF MYCN IN SHH TYPE TP53 MUTATED MB’S METABOLISM

BACKGROUND Medulloblastoma is classified in 4 subgroups. Prognosis and therapeutic option were 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 MYCN 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 MYCN in 507CSC and DAOY, proliferation assay, mRNA expression and measurements of ex-vivo metabolic phenotype were performed. RESULTS MYCN inhibition leads to cell death in both cell lines. MYCN regulated glucose, glutamine and methionine metabolism. Especially the targets were PKM2, GLS2, MAT2A, DNMT1 and 3A. CONCLUSION MYCN is a target of therapy in a patient with SHH type TP53 mutated medulloblastoma.