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Characterization of methylation profile during tumor progression of Wilms tumors

Grant number: 15/22758-8
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): January 01, 2016
Effective date (End): August 31, 2016
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Mariana Camargo Maschietto
Grantee:João Victor da Silva Guerra
Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil
Associated research grant:14/10250-7 - Characterization of the epigenetic regulation in human solid paediatric tumours, AP.JP


The embryonic Wilms tumors are tumors that exhibit morphological heterogeneity with three components: blastema, epithelia and stroma. Mutations in WT1, CTNNB1, WTX, DROSHA, SIX2, MYCN, TP53, and others less common genes overlap and are found in 30% of the analyzed cases. Moreover, the loss of imprinting of 11p15, resulting in overexpression of IGF2 is found in about 70% of cases. Alone, none of these changes are able to generate tumors in animal models. The DNA methylation is associated with the cell plasticity, that is, the ability of a cell to adapt to different conditions. The hypermethylation of CDH1 promoter is responsible for the repression of E-cadherin, which is regarded as the first step of the epithelial-mesenchymal transition associated with the formation of metastasis. The objective of this project is to characterize the methylation profiles in Wilms tumors, normal and their lung metastasis in order to identify the mechanisms involved with formation of metastasis. These samples were provided by the National Cancer Institute (INCA) in Rio de Janeiro, and will be hybridized in the plataform HM450K BeadChip (Illumina), which interrogates about 485,000 CpG sites. Cases came from formalin fixed paraffin embedded samples to allow a better morphological characterization of the cells. The DNA methylation changes will be explored, using methylation analysis packages available in Bioconductor (

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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)
GUERRA, JOAO V. S.; OLIVEIRA-SANTOS, JOSE; OLIVEIRA, DANYLLO F.; LEAL, GABRIELA F.; OLIVEIRA, JOAO RICARDO M.; COSTA, SILVIA S.; KREPISCHI, V, ANA C.; VIANNA-MORGANTE, ANGELA M.; MASCHIETTO, MARIANA. DNA methylation fingerprint of monozygotic twins and their singleton sibling with intellectual disability carrying a novel KDM5C mutation. EUROPEAN JOURNAL OF MEDICAL GENETICS, v. 63, n. 3, . (15/22758-8, 13/08028-1, 15/06281-7)

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