DNA methylation as a key epigenetic player for hepatoblastoma characterization.
Epigenetics
Hepatoblastoma
Hepatocyte differentiation
Methylation
Stratification
Journal
Clinics and research in hepatology and gastroenterology
ISSN: 2210-741X
Titre abrégé: Clin Res Hepatol Gastroenterol
Pays: France
ID NLM: 101553659
Informations de publication
Date de publication:
May 2021
May 2021
Historique:
received:
29
06
2020
revised:
04
03
2021
accepted:
18
03
2021
pubmed:
15
4
2021
medline:
8
2
2022
entrez:
14
4
2021
Statut:
ppublish
Résumé
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. 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. 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' 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. 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.
Sections du résumé
BACKGROUND
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
METHODS
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
RESULTS
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' 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
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.
Identifiants
pubmed: 33852955
pii: S2210-7401(21)00063-2
doi: 10.1016/j.clinre.2021.101684
pii:
doi:
Substances chimiques
CCAAT-Enhancer-Binding Proteins
0
Proto-Oncogene Proteins
0
Mixed Function Oxygenases
EC 1.-
TET1 protein, human
EC 1.-
UHRF1 protein, human
EC 2.3.2.27
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
101684Informations de copyright
Copyright © 2021 Elsevier Masson SAS. All rights reserved.