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TET Upregulation Leads to 5-Hydroxymethylation Enrichment in Hepatoblastoma.
Rivas, Maria Prates; Aguiar, Talita Ferreira Marques; Fernandes, Gustavo Ribeiro; Caires-Júnior, Luiz Carlos; Goulart, Ernesto; Telles-Silva, Kayque Alves; Cypriano, Monica; de Toledo, Silvia Regina Caminada; Rosenberg, Carla; Carraro, Dirce Maria; da Costa, Cecilia Maria Lima; da Cunha, Isabela Werneck; Krepischi, Ana Cristina Victorino.
Afiliação
  • Rivas MP; Human Genome and Stem-Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
  • Aguiar TFM; Human Genome and Stem-Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
  • Fernandes GR; International Center of Research, A. C. Camargo Cancer Center, São Paulo, Brazil.
  • Caires-Júnior LC; Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil.
  • Goulart E; Human Genome and Stem-Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
  • Telles-Silva KA; Human Genome and Stem-Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
  • Cypriano M; Human Genome and Stem-Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
  • de Toledo SRC; Department of Pediatrics, Support Group for Children and Adolescents With Cancer (GRAACC), Federal University of São Paulo, São Paulo, Brazil.
  • Rosenberg C; Department of Pediatrics, Support Group for Children and Adolescents With Cancer (GRAACC), Federal University of São Paulo, São Paulo, Brazil.
  • Carraro DM; Human Genome and Stem-Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
  • da Costa CML; International Center of Research, A. C. Camargo Cancer Center, São Paulo, Brazil.
  • da Cunha IW; Department of Pediatric Oncology, A. C. Camargo Cancer Center, São Paulo, Brazil.
  • Krepischi ACV; Department of Pathology, Rede D'Or São Luiz, São Paulo, Brazil.
Front Genet ; 10: 553, 2019.
Article em En | MEDLINE | ID: mdl-31249594
Hepatoblastoma is an embryonal liver tumor carrying few genetic alterations. We previously disclosed in hepatoblastomas a genome-wide methylation dysfunction, characterized by hypermethylation at specific CpG islands, in addition to a low-level hypomethylation pattern in non-repetitive intergenic sequences, in comparison to non-tumoral liver tissues, shedding light into a crucial role for epigenetic dysregulation in this type of cancer. To explore the underlying mechanisms possibly related to aberrant epigenetic modifications, we evaluated the expression profile of a set of genes engaged in the epigenetic machinery related to DNA methylation (DNMT1, DNMT3A, DNMT3B, DNMT3L, UHRF1, TET1, TET2, and TET3), as well as the 5-hydroxymethylcytosine (5hmC) global level. We observed in hepatoblastomas a general disrupted expression of these genes from the epigenetic machinery, mainly UHRF1, TET1, and TET2 upregulation, in association with an enrichment of 5hmC content. Our findings support a model of active demethylation by TETs in hepatoblastoma, probably during early stages of liver development, which in combination with UHRF1 overexpression would lead to DNA hypomethylation and an increase in overall 5hmC content. Furthermore, our data suggest that decreased 5hmC content might be associated with poor survival rate, highlighting a pivotal role of epigenetics in hepatoblastoma development and progression.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: Front Genet Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: Front Genet Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça