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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

TET Upregulation Leads to 5-Hydroxymethylation Enrichment in Hepatoblastoma

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Rivas, Maria Prates [1] ; Marques Aguiar, Talita Ferreira [2, 1] ; Fernandes, Gustavo Ribeiro [3] ; Caires, Luiz Carlos [1] ; Goulart, Ernesto [1] ; Telles-Silva, Kayque Alves [1] ; Cypriano, Monica [4] ; Caminada de Toledo, Silvia Regina [4] ; Rosenberg, Carla [1] ; Carraro, Dirce Maria [2] ; Lima da Costa, Cecilia Maria [5] ; da Cunha, Isabela Werneck [6] ; Victorino Krepischi, Ana Cristina [1]
Total Authors: 13
[1] Univ Sao Paulo, Inst Biosci, Dept Genet & Evolutionary Biol, Human Genome & Stem Cell Res Ctr, Sao Paulo - Brazil
[2] AC Camargo Canc Ctr, Int Ctr Res, Sao Paulo - Brazil
[3] Univ Sao Paulo, Dept Biochem Inst Chem, Sao Paulo - Brazil
[4] Univ Fed Sao Paulo, Dept Pediat Support Grp Children & Adolescents Ca, Sao Paulo - Brazil
[5] AC Camargo Canc Ctr, Dept Pediat Oncol, Sao Paulo - Brazil
[6] Rede Dor Sao Luiz, Dept Pathol, Sao Paulo - Brazil
Total Affiliations: 6
Document type: Journal article
Source: FRONTIERS IN GENETICS; v. 10, JUN 12 2019.
Web of Science Citations: 1

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. (AU)

FAPESP's process: 16/23462-8 - Epigenetic mechanisms in liver tumors: expression modulation of epigenetic gene regulators and gene expression analysis by RNAseq in hepatoblastoma.
Grantee:Maria Prates Rivas
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
Grantee:Mayana Zatz
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 17/16283-2 - Development of tissue bioengineering techniques for the functional reconstruction of ex vivo iPSC cell livers
Grantee:Luiz Carlos de Caires Júnior
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 15/14821-1 - Development of functional hepatic by-pass using iPSCs derived cells
Grantee:Ernesto da Silveira Goulart Guimarães
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 16/04785-0 - Study of somatic mutations identified in exome sequencing of hepatoblastoma
Grantee:Talita Ferreira Marques Aguiar
Support type: Scholarships in Brazil - Doctorate (Direct)