Integrative epigenomic analysis of gliomas: defining regulatory regions associated with stemness and with the hypermethylator phenotype of IDH1/2 mutant tumors

• Grant number: 18/00583-0
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: September 01, 2019
• End date: August 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Tathiane Maistro Malta Pereira
• Grantee: Tathiane Maistro Malta Pereira
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Ana Valeria Castro ; Fabíola Attié de Castro ; Houtan Noushmehr ; Sergio Akira Uyemura
• Associated scholarship(s): 25/02075-5 - Mapping Tumor Heterogeneity Using Epigenomic Data from Single-Cell Sequencing, BP.TT; 22/16350-0 - Mapping of tumor heterogeneity using epigenomic data from single cell sequencing, BP.TT; 22/11918-8 - Mapping stemness epigenomic signatures in gliomas, BP.IC; + associated scholarships 21/08190-0 - Mapping epigenomic signatures associated with IDH mutation, BP.IC; 21/00283-9 - Mapping tumor epigenomic signatures in gliomas: correlating glioma stem cells with clinical and molecular data, BP.MS; 20/13533-0 - Mapping transcriptomic signatures of tumor stem cells in gliomas: correlating glioma stem cells with clinical and molecular data, BP.MS; 20/09046-7 - Mapping stemness epigenomic signatures in gliomas, BP.IC; 20/05492-2 - Identification of regulatory regions associated with mutation in the IDH1/2 genes in different tumor types, BP.MS; 19/14928-1 - Integrative epigenomic analysis of gliomas - defining regulatory regions associated with stemness and with the hypermethylator phenotype of IDH1/2 mutant tumors, BP.JP - associated scholarships

Abstract

Adult malignant Gliomas are heterogeneous brain tumors characterized by recurrence and progression with variable patterns. Although some progress has been seen in the past years, Glioma field faces suboptimal disease classification, which may impact patient management and hinder the correct treatment. Mutation in the IDH genes, the hypermethylator G-CIMP phenotype and codeletion of chromosome arms 1p/19q are associated with subtypes of Gliomas and improve their classification. Notably, increasing evidence suggests that aberrant DNA methylation play a role in the development and/or progression of Gliomas. In glioblastomas, it is appreciated that differentiation status impacts tumor cell properties and that stem-like cells likely drive tumor progression and therapeutic resistance. We aim to perform a comprehensive and integrated epigenomic analysis to define the regulatory regions associated with stemness in Gliomas and with the hypermethylator phenotype of IDH1/2 mutation in Gliomas and across different tumor types. Our findings may provide: 1) elucidation of the mechanisms of tumorigenesis and tumor progression; 2) potential mechanisms related to the genome-wide DNA methylation and metabolism dysregulation in IDH1/2 mutant tumors; and 3) potential translational outcomes, such as identification of biomarkers that predict for progression and drug resistance, novel targets for drug development, refinement of existing molecular tumor classification allowing a better stratification for tailored treatment. Finally, this proposal will establish the innovative area of cancer epigenomics at FCFRP, which will allow important collaboration and contribute to expanding the research actions at FCFRP. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LARISSA MIYUKI OKANO; LÍVIA MARIA MACIEL DA FONSECA; ISABELA DIAS ERTHAL; TATHIANE MAISTRO MALTA. Epigenomic integrative analysis pinpoint master regulator transcription factors associated with tumorigenesis in squamous cell carcinoma of oral tongue. GENETICS AND MOLECULAR BIOLOGY, v. 46, n. 2, 2023-06-19. (21/08190-0, 18/00583-0, 19/14928-1)

XAVIER, PEDRO L. P.; MARCAO, MAYCON; SIMOES, RENAN L. S.; JOB, MARIA EDUARDA G.; STREFEZZI, RICARDO DE FRANCISCO; FUKUMASU, HEIDGE; MALTA, TATHIANE M.. Machine learning determines stemness associated with simple and basal-like canine mammary carcinomas. HELIYON, v. 10, n. 5, p. 12-pg., 2024-02-28. (23/07358-0, 18/00583-0, 23/05099-7, 22/06305-7, 19/14928-1, 22/09378-5, 21/00283-9)

MALTA, TATHIANE M.; SABEDOT, THAIS S.; MOROSINI, NATALIA S.; DATTA, INDRANI; GAROFANO, LUCIANO; VALLENTGOED, WIES; VARN, FREDERICK S.; ALDAPE, KENNETH; D'ANGELO, FULVIO; BAKAS, SPYRIDON; et al. The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen. Cancer Research, v. 84, n. 5, p. 16-pg., 2024-03-04. (19/14928-1, 18/00583-0)