DNA methylation as a key epigenetic player for hepatoblastoma characterization

Autor(es):Mostrar menos -

Rivas, Maria ^[1] ; Aguiar, Talita ^{[1, 2]} ; Fernandes, Gustavo ^[1] ; Lemes, Renan ^[1] ; Caires-Junior, Luiz ^[1] ; Goulart, Ernesto ^[1] ; Telles-Silva, Kayque ^[1] ; Maschietto, Mariana ^[3] ; Cypriano, Monica ^[4] ; de Toledo, Silvia ^[4] ; Carraro, Dirce ^[5] ; da Cunha, Isabela ^[6] ; da Costa, Cecilia ^[7] ; Rosenberg, Carla ^[1] ; Krepischi, Ana ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biosci, Dept Genet & Evolutionary Biol, Human Genome & Stem Cell Res Ctr, Sao Paulo, SP - Brazil

^[2] NYU Grossman Sch Med, Dept Urol, New York, NY - USA

^[3] Boldrini Childrens Hosp, Res Ctr, Campinas - Brazil

^[4] Univ Fed Sao Paulo, Adolescent & Child Canc Support Grp GRAACC, Dept Pediat, Sao Paulo, SP - Brazil

^[5] AC Camargo Canc Ctr, Int Ctr Res, Sao Paulo, SP - Brazil

^[6] Rede D OR Sao Luiz, Pathol Dept, Sao Luis, SP - Brazil

^[7] AC Camargo Canc Ctr, Dept Pediat Oncol, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY; v. 45, n. 3 MAY 2021.
• Citações Web of Science: 0

Resumo

Background: Hepatoblastoma (HB) is a rare embryonal liver tumor of children. Although intrinsic biological differences between tumors can affect prognosis, few groups have studied these differences. Given the recent increased attention to epigenetic mechanisms in the genesis and progression of these tumors, we aimed to classify HB samples according to the stages of liver development and DNA methylation machinery. Basic procedures: We evaluated the expression of 24 genes associated with DNA methylation and stages of hepatocyte differentiation and global DNA methylation. Using bioinformatics tools and expression data, we propose a stratification model for HB. Main findings: Tumors clustered into three groups that presented specific gene expression profiles of the panel of DNA methylation enzymes and hepatocyte differentiation markers. In addition to reinforcing these embryonal tumors \& rsquo; molecular heterogeneity, we propose that a panel of 13 genes can stratify HBs (TET1, TET2, TET3, DNMT1, DNMT3A, UHRF1, ALB, CYP3A4, TDO2, UGT1A1, AFP, HNF4A, and FOXA2). DNA methylation machinery participates in the characterization of HBs, directly reflected in diverse DNA methylation content. The data suggested that a subset of HBs were similar to differentiated livers, with upregulation of mature hepatocyte markers, decreased expression of DNA methylation enzymes, and higher global methylation levels; these findings might predict worse outcomes. Conclusions: HBs are heterogeneous tumors. Despite using a small cohort of 21 HB samples, our findings reinforce that DNA methylation is a robust biomarker for this tumor type. (c) 2021 Elsevier Masson SAS. All rights reserved. (AU)

• Processo FAPESP: 16/23462-8 - Estudo de mecanismos epigenéticos em tumores de fígado: modulação da expressão de genes reguladores da epigenética e análise de expressão gênica por RNAseq em hepatoblastoma.
• Beneficiário: Maria Prates Rivas
• Modalidade de apoio: Bolsas no Brasil - Doutorado