Characterization of the mechanisms involved with distinct methylation profiles between subgroups of osteosarcomas

• Grant number: 24/20428-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Mariana Camargo Maschietto
• Grantee: Walquíria Fernandes Venancio
• Host Institution: Centro Infantil de Investigações Hematológicas Dr Domingos A Boldrini (CIB). Campinas , SP, Brazil
• Associated research grant: 21/06782-7 - Striking the evolutionary process of bone tumors, AP.JP2

Abstract

Osteosarcomas are bone tumors that can arise in the pediatric age. Approximately 25% of cases present with lung metastasis at diagnosis and 50% of the remaining cases present with metastasis during the follow-up of the disease, which contributes to the high mortality rates. The genomic profiles of osteosarcomas present a high number of structural alterations, which include copy number alterations (CNAs), translocations, small insertions/deletions (indels) and complex events such as chromoanasynthesis and chromothripsis. However, osteosarcomas have few recurrently mutated genes (such as TP53, RB1, CDKN2A, MYC, CCNE1, TGFB1). Osteosarcomas present intra- and intertumoral genetic heterogeneity, that is, tumors from different individuals are quite distinct from a genomic point of view and within a tumor, several clones characterized by distinct mutational events coexist. For these reasons, genetic characteristics associated with the prognosis of patients with osteosarcoma have not been described to date, which has also impacted the search for therapies based on genetic alterations. Several studies have associated epigenetic profiles with specific tumor types, including bone sarcomas, occasionally pointing to new tumor classes. In this line, a previous study by our group found two groups of osteosarcomas based on methylation profiles. In a more detailed analysis, these groups also present differences in the number of CNAs, both focal and chromosomal. This study aims to characterize the epigenetic mechanisms that may be involved in the subgroups of osteosarcomas. To this end, the DNA methylation profiles of osteosarcomas will be specific in relation to gene expression and histone modifications.