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Characterization of the epigenetic regulation in human solid paediatric tumours

Abstract

Pediatric solid tumors comprise 3% of all cancers with approximately 70% of these children becoming adults. The treatment of tumors with poorer prognosis has already reached the limits of tolerance requiring the search for alternative therapies. On the other hand, around one in every 750-1000 adults are survivors of cancer in the childhood and suffer late adverse effects from the aggressive treatment they received. The comprension of the biological mechanisms involved with the onset and progression of pediatric tumors is essential to assist in the diagnosis, estimate the prognosis of these patients and develop new treatment strategies. In this study, Wilms tumours and osteosarcomas will be used as models to study the involvement of epigenetic changes with cell transformation in paediatric tumours. The detection of aberrantly methylated genes throughout the genome may help to understand the biology involved in cellular transformation and point out possible candidates for prognostic or therapeutic biomarkers. The purpose of this project is to investigate the global epigenetic dysregulation that occurs in Wilms tumours and osteosarcomas to give insights into the mechanisms involved with cell malignant transformation. For this, a high-coverage microarray will be used to characterize and quantify differences in the methylation level between primary tumors and the respective normal tissues. Once we identify sequences found methylated exclusively in the tumors, detection of these might be tested in the peripheral blood of the patients through high-depth sequencing as potential diagnostic markers. This study requires integration of a wide range of areas, since the use of clinical data, histological analyses of the samples, methylation experiments, high-deph sequencing and bioinformatics, with the potential of establishing a new research area at LNBio. (AU)

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Scientific publications (5)
(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)
DE SA PEREIRA, BRUNA MARIA; MONTALVAO DE AZEVEDO, RAFAELA; DA SILVA GUERRA, JOAO VICTOR; FARIA, PAULO A.; SOARES-LIMA, SHEILA COELHO; DE CAMARGO, BEATRIZ; MASCHIETTO, MARIANA. Non-coding RNAs in Wilms' tumor: biological function, mechanism, and clinical implications. JOURNAL OF MOLECULAR MEDICINE-JMM, v. 99, n. 8, p. 1043-1055, . (14/10250-7, 15/06281-7)
PIRES, SARA FERREIRA; DE BARROS, JULIANA SOBRAL; DA COSTA, SILVIA SOUZA; DO CARMO, GABRIEL BANDEIRA; SCLIAR, MARILIA DE OLIVEIRA; LENGERT, ANDRE VAN HELVOORT; BOLDRINI, ERICA; DA SILVA, SANDRA REGINI MORINI; VIDAL, DANIEL ONOFRE; MASCHIETTO, MARIANA; et al. Analysis of the Mutational Landscape of Osteosarcomas Identifies Genes Related to Metastasis and Prognosis and Disrupted Biological Pathways of Immune Response and Bone Development. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 13, p. 22-pg., . (13/08028-1, 14/10250-7, 18/21047-9)
PIRES, SARA FERREIRA; DE BARROS, JULIANA SOBRAL; DA COSTA, SILVIA SOUZA; SCLIAR, MARILIA DE OLIVEIRA; LENGERT, ANDRE VAN HELVOORT; BOLDRINI, ERICA; MORINI DA SILVA, SANDRA REGINA; TASIC, LJUBICA; VIDAL, DANIEL ONOFRE; VICTORINO KREPISCHI, ANA CRISTINA; et al. DNA methylation patterns suggest the involvement of DNMT3B and TET1 in osteosarcoma development. Molecular Genetics and Genomics, v. 298, n. 3, p. 13-pg., . (15/06281-7, 18/06510-4, 18/24069-3, 14/10250-7)
QUINTERO ESCOBAR, MELISSA; CARNEIRO COSTA, TASSIA BRENA BARROSO; MARTINS, LUCAS G.; COSTA, SILVIA S.; VANHELVOORT LENGERT, ANDRE; BOLDRINI, ERICA; MORINI DA SILVA, SANDRA REGINA; FERNANDO LOPES, LUIZ; ONOFRE VIDAL, DANIEL; KREPISCHI, V, ANA C.; et al. Insights in Osteosarcoma by Proton Nuclear Magnetic Resonance Serum Metabonomics. FRONTIERS IN ONCOLOGY, v. 10, . (18/21047-9, 18/06510-4, 15/06281-7, 14/10250-7)
TASIC, LJUBICA; AVRAMOVIC, NATASA; QUINTERO, MELISSA; STANISIC, DANIJELA; MARTINS, LUCAS G.; DA COSTA, TASSIA BRENA BARROSO CARNEIRO; JADRANIN, MILKA; DE SOUZA ACCIOLY, MARIA THERESA; FARIA, PAULO; DE CAMARGO, BEATRIZ; et al. A Metabonomic View on Wilms Tumor by High-Resolution Magic-Angle Spinning Nuclear Magnetic Resonance Spectroscopy. DIAGNOSTICS, v. 12, n. 1, . (14/10250-7, 18/24069-3, 18/06510-4)

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