MBCL-30. NOVEL SMO MUTATION IN DESMOPLASTIC/NODULAR MEDULLOBLASTOMA: A CASE REPORT

Smoothened (SMO) is a transmembrane protein which is regulated by SHH (Sonic hedgehog) protein binding to PTCH1. SMO activation controls GLI which then translocates into the nucleus and activates target genes. The SHH subtype of medulloblastoma has been extensively studied to have mutations within the SHH signaling pathway, often in PTCH1, SUFU, and SMO. We present a case of desmoplastic/nodular medulloblastoma with the mutation SMO c.1810G>A. The patient presented at 11 years old with a two-week history of headaches and morning vomiting. His neuroimaging revealed a T2 hyperintense, enhancing mass centered at the fourth ventricle. He underwent gross total resection and had no metastatic spread. There were no alterations in PTCH1, SUFU, Tp53, GLI2, MYC/MYCN, CTNNB1, or the WNT pathway. The SMO c.1810G>A alteration has not been previously identified as a somatic mutation in a CNS tumor. The functional effect of this mutation has not been studied. It is known that desmoplastic/nodular histology in medulloblastoma is associated with the SHH subtype and given the fact that SMO is regulated by SHH signaling, this patient was ultimately diagnosed with SHH subtype medulloblastoma. Findings of novel somatic mutations in patients raises the question of whether the mutation is in fact the driver of neoplasia.