HGG-21. GERMLINE MUTATIONS IN MSH2 GENE IN PEDIATRIC PATIENTS WITH CONGENITAL AND SPORADIC GLIOBLASTOMA

Abstract

INTRODUCTIONGlioblastoma (GBM) remains one of the biggest therapeutic challenges in neuro-oncology. In spite of multimodal treatment approaches the prognosis of GBM is extremely poor, median survival is estimated about 12–16 months. Although GBM is one of the most common and malignant primary brain tumors, pediatric glioblastoma, including congenital is a very rare tumor, with an incidence of about 1.1–3.4 per million live births. Moreover, the mode of presentation, behavior, response to therapy and molecular background of pediatric glioblastomas differs from adult type of GBM. Until now, about ten patients with congenital glioblastoma have been described and in none of them germline markers were examined. Here we report two patients with GBM, one with congenital tumor with germline mutations in MSH2 gene.METHODSTargeted Next-Generation Sequencing (NGS) of the probands DNA extracted from leucocytes was performed using the TruSight One sequencing panel on an Illumina HiSeq 1500. Applied gene panel investigated the coding sequence and splice sites of 4813 genes associated with known disease phenotypes. The NGS data were analyzed using an in-house procedure. Identified variants were validated by Sanger sequencing.RESULTSNGS analysis of patients constitutional DNA revealed know, pathogenic variants c.940C>T and c.942 + 3A>T in MSH2 gene (NM_000251.3) associated with MMR-dependent hereditary cancer syndromes.CONCLUSIONMolecular analysis are heavily needed for better understanding of pediatric GBM etiology and new treatment modality implementation. Identification of this oncogenic driver may provide insight into the pathogenesis of GBM, including congenital cases. Funded by National Science Centre, Poland (2016/23/B/NZ2/03064 and 2016/21/B/NZ2/01785).