Abstract 2248: Osteosarcoma under the age of 10: using next-generation sequencing panel for tumor profile investigation
Authors: Guimarães Giovanna M. , Gamba Francine Tesser , Petrilli Antônio Sérgio , Alves Maria Teresa S. , Garcia-Filho Reinaldo J. , de Oliveira Renato , Toledo Sílvia Regina C. 
Published: July 2021

Abstract
Background: Osteosarcoma (OS) is the most-common primary bone tumor among children and adolescents, presenting a high risk of metastasis. Despite the OS incidence peak in the second decade of life, it has been shown that a significant number of children are diagnosed with less than 10 years of age. The investigation of possible biological and clinical particularities in this group of patients can contribute to a better understanding of OS tumorigenesis and to development of a more personalized therapeutic and clinical management. The aim of this study is to identify genetic alterations in children diagnosed with OS in an unexpected age using next-generation sequencing (NGS) strategy.
Methods: Thirty OS samples from 30 patients who were under the age of 10 at the time of diagnosis, treated at the Pediatric Oncology Institute GRAACC/UNIFESP, were submitted to NGS using a specific panel for childhood and adolescent neoplasm named OCCRA (Oncomine Childhood Cancer Research Assay), from Thermo Fisher. Clinical variables have also been collected.
Results: Of the 30 samples analyzed 16 (53.3%) presented some genetic alteration. The most commonly genetic alteration identified was CNVs in the MYC gene, a proto-oncogene that has already been associated with worse prognosis and response to treatment in OS cases. All 6 patients with MYC amplification presented bad response to treatment. ARID1A tumor suppressor gene was the second-most commonly mutated, with 4 patients presenting loss-of-function InDels, not reported in COSMIC database. We also identified 3 patients with CDK4 CNVs classified as gain-of-function alterations and 3 patients with loss-of-function TP53 alterations, 2 SNVs and 1 InDel. Two of the identified variants in TP53 have not yet been reported in COSMIC database. Of the 3 patients harboring TP53 variants, one has Li-Fraumeni syndrome confirmed.
Conclusions: The genetic profiling based on a specific panel for children and adolescent cancer, including non-reported variants identification in patients diagnosed with OS in an unexpected age, is essential for a more accurate tumor profiling and the identification of risk groups. The investigation of mutations with clinical relevance can also contribute to a more precise therapeutic management. NGS strategy can lead into a better understanding about these questions.
Funding Source: São Paulo Research Foundation (FAPESP) - n° 2019/13056-0
Citation Format: Giovanna M. Guimarães, Francine Tesser Gamba, Antônio Sérgio Petrilli, Maria Teresa S. Alves, Reinaldo J. Garcia-Filho, Renato de Oliveira, Sílvia Regina C. Toledo. Osteosarcoma under the age of 10: using next-generation sequencing panel for tumor profile investigation [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 2248.