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Chromatin accessibility and DNA methylation changes associated with high and low Glioma-CpG island methylator phenotype (G-CIMP)

Grant number: 16/12329-5
Support Opportunities:Scholarships abroad - Research Internship - Doctorate (Direct)
Effective date (Start): October 01, 2016
Effective date (End): September 30, 2017
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Houtan Noushmehr
Grantee:Thaís Sarraf Sabedot
Supervisor: Laila M. Poisson
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Research place: Henry Ford Health System, United States  
Associated to the scholarship:16/06488-3 - Integrative epigenomic analysis of high and low Glioma-CpG island Methylator Phenotype (G-CIMP): characterization and methods development, BP.DD


Malignant gliomas are quite heterogeneous brain tumors characterized by progression and recurrence with highly variable patterns and intervals. The World Health Organization established both histological and molecular features to classify gliomas in 2016, being IDH mutation the most predictive biomarker. So far, this alteration was associated with favorable clinical outcome and increased DNA methylation levels at CpG islands (G-CIMP). However, a recent study showed a subclassification for G-CIMP tumors: G-CIMP-low, with a lower DNA methylation profile associated with significantly worse survival and abnormalities in cell cycle pathway genes, and G-CIMP-high, with higher global levels of DNA methylation and better clinical outcome. Moreover, there are evidences showing a potential progression from G-CIMP-high to G-CIMP-low. The aim of this project is to study the progression mechanism through G-CIMP samples using Whole Genome Bisulfite Sequencing (WGBS) to assess changes in DNA methylation that may lead to alterations in chromatin accessibility, therefore, causing deregulation of coding genes. This effort will require generation of new data and integration with publicly available data in order to achieve better understanding of the epigenetic landscape from G-CIMP-low and G-CIMP-high samples. (AU)

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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)
MALTA, TATHIANE M.; SOKOLOV, ARTEM; GENTLES, ANDREW J.; BURZYKOWSKI, TOMASZ; POISSON, LAILA; WEINSTEIN, JOHN N.; KAMINSKA, BOZENA; HUELSKEN, JOERG; OMBERG, LARSSON; GEVAERT, OLIVIER; et al. Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation. Cell, v. 173, n. 2, p. 338+, . (16/06488-3, 14/08321-3, 15/07925-5, 16/01975-3, 16/01389-7, 16/15485-8, 14/02245-3, 16/10436-9, 16/12329-5)
DE SOUZA, CAMILA FERREIRA; SABEDOT, THAIS S.; MALTA, TATHIANE M.; STETSON, LINDSAY; MOROZOVA, OLENA; SOKOLOV, ARTEM; LAIRD, PETER W.; WIZNEROWICZ, MACIEJ; IAVARONE, ANTONIO; SNYDER, JAMES; et al. A Distinct DNA Methylation Shift in a Subset of Glioma CpG Island Methylator Phenotypes during Tumor Recurrence. CELL REPORTS, v. 23, n. 2, p. 637-651, . (14/03989-6, 16/15485-8, 16/06488-3, 14/08321-3, 16/12329-5, 16/01975-3, 14/02245-3, 15/07925-5)
MALTA, TATHIANE M.; DE SOUZA, CAMILA F.; SABEDOT, THAIS S.; SILVA, TIAGO C.; MOSELLA, MARITZA S.; KALKANIS, STEVEN N.; SNYDER, JAMES; CASTRO, ANA VALERIA B.; NOUSHMEHR, HOUTAN. Glioma CpG island methylator phenotype (G-CIMP): biological and clinical implications. NEURO-ONCOLOGY, v. 20, n. 5, p. 608-620, . (16/06488-3, 16/15485-8, 14/08321-3, 16/12329-5, 16/10436-9, 15/07925-5, 16/01975-3, 14/02245-3, 16/01389-7, 16/11039-3)

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