Epigenetic regulation of energy metabolism in tumors with mutation in the isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) genes

• Grant number: 22/06806-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2024
• End date: April 30, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Tathiane Maistro Malta Pereira
• Grantee: Lívia Maria Maciel da Fonseca
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Mutations in isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) genes are present in the vast majority of low-grade gliomas and less frequently in glioblastoma, acute myeloid leukemia, cholangiocarcinoma, among others. Aberrant epigenetic reprogramming is a documented feature of cancer and is even more prominent in tumors with mutations in IDH1 and IDH2 (IDH1/2), where an accumulation of global DNA methylation is observed in the genome, with a significant impact on the regulation of expression genetics. Epigenome remodeling in these tumors is also associated with changes in cellular energy metabolism, which has implications for tumor evolution and patient prognosis; however, the epigenetic regulation of metabolism resulting from mutated IDH1/2 is poorly understood. In this project, we propose to investigate the epigenetic regulation of cellular metabolism in tumors with a mutation in IDH1/2 genes using epigenomic data, computational tools, and functional assays. Our findings will contribute to the elucidation of the mechanisms that lead to the dysregulation of global DNA methylation and metabolism in tumors with a mutation in IDH1/2, and its biological implications for the treatment of this group of tumors.