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Genetic and epigenetic anomalies in the childhood tumor hepatoblastoma

Grant number: 11/24007-9
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): March 01, 2012
Effective date (End): October 31, 2014
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Carla Rosenberg
Grantee:Tatiane Cristina Rodrigues
Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:09/00898-1 - Submicroscopic genomic imbalances associated with specific congenital abnormalities and mental deficiency phenotypes, AP.TEM


During embryonic development, an anomalous signal may result in modifications or impairment of cell differentiation and maturation. Such molecular failures during morphogenesis may be points of initiation of childhood tumors, defined as tumors originating in the primary cells that have suffered genetic mutations. Hepatoblastoma (HB) is the most common liver cancer in children and adolescents, consisting of a solid embryonal tumor that presents in most cases high mortality and rapid progression. Hepatoblastomas have very heterogeneous morphology, which recapitulates the various stages of differentiation of the liver. Molecular data for the development of HBs are still rare. In this project we will evaluate three fundamental aspects for the correlation between genotyping and phenotyping in cancer: (1) gains and losses of genetic segments (Somatic Copy Number Alterations - SCNA) to be identified by comparative genomic hybridization in microarrays platform 180K (array-CGH); (2) analysis of gene mutations in coding regions of the genome by sequencing the exome (exome next-generation sequencing), and (3) changes in the pattern of methylation of DNA sequences distributed throughout the genome (genome wide methylation analysis) detected by using Illumina 450K BeadArrays. These tests will be performed in paired samples of hepatoblastomas and normal liver tissue to identify somatic mutations that are involved in carcinogenesis. Our hypothesis is that the identification of genetic pathways involved in hepatoblastoma may contribute to a better understanding of the disruption of normal differentiation of the liver and subsequent development of the carcinogenic process. (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)
FIDALGO, FELIPE; RODRIGUES, TATIANE CRISTINA; PINILLA, MABEL; SILVA, AMANDA GONCALVES; DO SOCORRO MACIEL, MARIA; ROSENBERG, CARLA; DE ANDRADE, VICTOR PIANA; CARRARO, DIRCE MARIA; VICTORINO KREPISCHI, ANA CRISTINA. Lymphovascular invasion and histologic grade are associated with specific genomic profiles in invasive carcinomas of the breast. TUMOR BIOLOGY, v. 36, n. 3, p. 1835-1848, . (12/21932-6, 08/57887-9, 11/24007-9)
RODRIGUES, TATIANE CRISTINA; FIDALGO, FELIPE; LIMA DA COSTA, CECILIA MARIA; FERREIRA, ELISA NAPOLITANO; DA CUNHA, ISABELA WERNECK; CARRARO, DIRCE MARIA; VICTORINO KREPISCHI, ANA CRISTINA; ROSENBERG, CARLA. Upregulated genes at 2q24 gains as candidate oncogenes in hepatoblastomas. FUTURE ONCOLOGY, v. 10, n. 15, p. 2449-2457, . (06/00054-0, 09/00898-1, 13/08028-1, 11/24007-9)
MASCHIETTO, MARIANA; RODRIGUES, TATIANE CRISTINA; KASHIWABARA, ANDRE YOSHIAKI; SOUZA DE ARAUJO, ERICA SARA; MARQUES AGUIAR, TALITA FERREIRA; LIMA DA COSTA, CECILIA MARIA; DA CUNHA, ISABELA WERNECK; VASQUES, LUCIANA DOS REIS; CYPRIANO, MONICA; BRENTANI, HELENA; et al. DNA methylation landscape of hepatoblastomas reveals arrest at early stages of liver differentiation and cancer-related alterations. ONCOTARGET, v. 8, n. 58, p. 97871-97889, . (15/06281-7, 09/00898-1, 16/04785-0, 13/08028-1, 11/24007-9)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
RODRIGUES, Tatiane Cristina. Genetic and epigenetic abnormalities in the embryonal tumor hepatoblastoma. 2015. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB) São Paulo.

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