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Molecular profiling of congenital glioblastoma using a next-generation sequencing panel
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  • Débora Cabral de Carvalho Corrêa,
  • Francine Tesser-Gamba,
  • Nasjla Saba da Silva,
  • Andrea Maria Capellano,
  • Maria Teresa de Seixas Alves,
  • Patrícia Alessandra Dastoli,
  • Marcos Devanir Silva da Costa,
  • Sergio Cavalheiro,
  • Silvia Regina Caminada de Toledo
Débora Cabral de Carvalho Corrêa
Pediatric Oncology Institute-GRAACC/UNIFESP
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Francine Tesser-Gamba
Pediatric Oncology Institute-GRAACC/UNIFESP
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Nasjla Saba da Silva
Pediatric Oncology Institute-GRAACC/UNIFESP
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Andrea Maria Capellano
Pediatric Oncology Institute-GRAACC/UNIFESP
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Maria Teresa de Seixas Alves
Federal University of Sao Paulo
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Patrícia Alessandra Dastoli
Pediatric Oncology Institute-GRAACC/UNIFESP
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Marcos Devanir Silva da Costa
Pediatric Oncology Institute-GRAACC/UNIFESP
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Sergio Cavalheiro
Pediatric Oncology Institute-GRAACC/UNIFESP
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Silvia Regina Caminada de Toledo
Pediatric Oncology Institute-GRAACC/UNIFESP
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Abstract

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 H3F3ATP53 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.