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Charting Epigenomic Signatures in CpG Island Methylator Phenotype (CIMP) Tumors

Grant number: 16/11039-3
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2017
Effective date (End): February 29, 2020
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Houtan Noushmehr
Grantee:Maritza Queiroz Salas Mosella
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:15/07925-5 - Open source software statistical tools to aid in analyzing and integrating large cancer epigenomic datasets in order to decipher and understand regulatory networks, AP.JP
Associated scholarship(s):17/10357-4 - Comprehensive and Integrative Methylome Analysis Across Endocrine Tumors Harboring the CpG Island Methylator Phenotype (CIMP), BE.EP.DR


DNA methylation is a process involved in gene stability, genomic organization and developmental process and has being associated with many diseases, such as cancer. In cancer, a genome-wide hypomethylation at non-promoters and focal hypermethylation at given CpG islands (promoters) are observed, responsible for overexpression of oncogenes and silencing of tumor suppressor genes, respectively. Accordingly to differential DNA methylation analyses, colorectal cancer was described to present the CpG island methylator phenotype (CIMP), characterized by widespread hypermethylation of CpG islands. CIMP phenotype has also been described in a myriad of distinct tumors. The most consolidated between them, the adrenal (A-CIMP), breast (B-CIMP), colorectal (C-CIMP) and gliomas (G-CIMP) will be the focus of this work. Despite presenting commonalities across tumors, CIMP points to specific tumor features, being related with good and bad prognosis. Dr. Noushmehr and colleagues first defined the G-CIMP and recently two novel subsets of G-CIMP, termed G-CIMP high and G-CIMP low, subclassification that also applies for other tumor types. Besides the impact of gene promoter, distal regulatory regions such as enhancers, silencers and boundary elements play an important role in the control of gene expression. Recent studies with C-CIMP points to protein-protein interactome as biomarkers to delineate CIMP/non-CIMP phenotypes. Despite CIMP have been extensively exploited, integration between CIMP and genome-wide regulatory element landscapes and transcription factor networks remains to be elucidated. In the current study we plan to perform a comprehensive differential integrative omics analyses across CIMP tumors regarding methylome both in promoter as well as in non-promoter regions.

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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.; 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)
MOSELLA, MARITZA S.; SABEDOT, THAIS S.; SILVA, TIAGO C.; MALTA, TATHIANE M.; DEZEM, FELIPE SEGATO; ASMARO, KARAM P.; WELLS, MICHAEL; MUKHERJEE, ABIR; POISSON, LAILA M.; SNYDER, JAMES; et al. DNA methylation-based signatures classify sporadic pituitary tumors according to clinicopathological features. NEURO-ONCOLOGY, v. 23, n. 8, p. 1292-1303, . (16/11039-3, 14/03989-6, 17/10357-4)

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