Molecular profiling of congenital glioblastoma using a next-generation sequencing panel

Background: Congenital glioblastoma (cGBM), presenting prenatally or within the first months of life, is among the rarest type of congenital brain tumor, with approximately 120 cases reported. Due to its infrequent occurrence, few studies have focused on the molecular and genetic aspects of this tumor, and the mutational events involved in the pathogenesis and progression of cGBM still remain poorly understood. This study aimed to investigate molecular alterations, with a potential prognostic marker and therapeutic target in cGBM using the next-generation sequencing (NGS) strategy.  Methods: We selected seven tumor samples from patients diagnosed with cGBM and treated at Pediatric Oncology Institute-GRAACC/UNIFESP. NGS was performed to identify somatic genetic variants in tumor samples using the Oncomine Childhood Cancer Research Assay panel, from ThermoFisher Scientific, designed specifically for pediatric neoplasms.  Results: Of all seven patients analyzed, three patients exhibited tumors with genetic variants, which include two pathogenic variants in  NF1 and  SUZ12 genes that have not been reported in cGBM yet, an increase in the number of copies of  ALK gene, and two gene fusions,  PPP1CB-ALK and  TPM3-NTRK1 . Also, none of the cases showed variants in  H3F3A ,  TP53 and  ATRX genes, alterations which are frequently seen in pediatric and adolescent GBM.  Conclusions: Our results suggest that cGBM may comprise a unique tumor entity and alterations in  ALK and  NTRK genes provide a potential target for therapy. Therefore, identification of genetic variants in cGBM is highly relevant in order to define prognosis and therapeutic strategies.