Abstract 2167: Genomic profiling of pediatric and adolescent ependymomas: Underlying genetic alterations for prognosis and therapeutic orientation
Authors: de Corrêa Débora Cabral , Oliveira Indhira Dias , Tesser-Gamba Francine , de Seixas Alves Maria Teresa , Saba-Silva Nasjla , Capellano Andrea Maria , Dastoli Patrícia , Cavalheiro Sergio , de Toledo Silvia Regina Caminada 
Published: July 2021

Abstract
Background: Ependymoma (EPN) is the third most common brain tumor in children and adolescents and is incurable in up to 40% cases, as chemotherapy is ineffective in most individuals and treatment remains challenging. A genetic panel based on next-generation sequencing (NGS) technology and developed exclusively for pediatric neoplasms is essential in order to determine prognosis and therapeutic managements in EPN, as this tumor comprise several molecular subgroups with unique clinical characteristics. We aimed to detect and investigate molecular alterations, with potential prognostic marker and therapeutic target in childhood and adolescence EPN, using the NGS strategy.
Methods: We selected 59 EPN samples from patients diagnosed and treated at Pediatric Oncology Institute-GRAACC/UNIFESP. All 59 EPN samples were divided according to the anatomical compartment of the Central Nervous System: 41 samples from the posterior fossa (PF), 13 supratentorial (ST) and 5 spinal (SP). NGS was performed to identify somatic genetic alterations in tumor samples using Oncomine Childhood Cancer Research Assay (OCCRA) panel, from Thermo Fisher, designed specifically for childhood and adolescence neoplasms. Our molecular findings were correlated with clinical and histopathological characteristics of the patients analyzed.
Results: A total of 59 EPN samples were sequenced in our institution and we identified somatic alterations in 24 of 59 (40.7%) tumors. We observed 14 altered genes and 16 genetic variants, which 43.8% were pathogenic and 37.5% have not been reported yet. The most commonly detected genetic alterations were involving ASXL1, CIC, JAK2, ABL2 and MDM4 genes. SNVs were the majority of all genetic alterations detected, accounting for 10 of 20 cases (50%). The pathogenic and synonymous mutation c.4533C&gt;T of CIC gene, previously reported as SNP, was the most frequent variant observed in EPN samples. CNVs were observed in ABL2 and MDM4 genes and were exclusively identified in PF-EPN samples. Gene fusions were found in 3 alive patients with age to diagnosis under 5 years and with ST-EPN and SP-EPN.
Conclusions: Molecular profile investigation, based on NGS panel specific for pediatric tumors, can provide information about potential prognostic biomarkers for EPN. Thus, genomic profiling of childhood and adolescence EPN that appropriately integrate the clinical, radiologic, and histologic aspects of this tumor, is essential in order to define therapeutic strategies.
Funding Source: São Paulo Research Foundation (FAPESP no. 2019/12074-5)
Citation Format: Débora Cabral de Corrêa, Indhira Dias Oliveira, Francine Tesser-Gamba, Maria Teresa de Seixas Alves, Nasjla Saba-Silva, Andrea Maria Capellano, Patrícia Dastoli, Sergio Cavalheiro, Silvia Regina Caminada de Toledo. Genomic profiling of pediatric and adolescent ependymomas: Underlying genetic alterations for prognosis and therapeutic orientation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2167.