ArticleJournal of hepatology2020
Epigenetic footprint enables molecular risk stratification of hepatoblastoma with clinical implications.
Article in Journal of hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 2 of them syntheses that pooled it.
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Who cites it
91 citing papers in PubMed, 2 syntheses or guidelines pooled it, 140 citations in OpenAlex.
- Hepatoblastoma: an investigation of diagnostic, prognostic, and therapeutic gene targets and biomarkers.Pediatric research · 2026Pooled it
- Multiancestry Transcriptome-Wide Association Study Identifies Candidate Genes Associated with Hepatoblastoma.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2025Pooled it
- Open Questions in Surgery for Hepatoblastoma: A Joined SIOPEL-IPSO Survey.European journal of haematology · 2026Article
- Article
- Differential Wnt/β-catenin signaling via TCF7L2/LEF1 binding specificity shapes cellular and tumor phenotypes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Preclinical Drug-Response Profiling Identifies BMI1 Inhibition as a Therapeutic Option for Hepatoblastoma.International journal of molecular sciences · 2026Article
- Article
- Proteasome Targeting with Carfilzomib Induces Reactive Oxygen Species-Mediated Apoptosis in Hepatoblastoma.Cells · 2026Article
- Effective therapeutic targeting of CTNNB1-mutant hepatoblastoma with WNTinib.Molecular oncology · 2026Article
- Trefoil Factor-3 Is a Hypoxia-Triggered Pro-Tumorigenic Factor in Hepatoblastoma.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Reversible dissociation of mitochondrial Complex V balances anabolic and energy-generating needs in cancer.iScience · 2026Article
- Proteomic analysis reveals the pro-proliferative role of the LIN28B/HMGA2 axis in hepatoblastoma.Pediatric surgery international · 2026Article
- EZH2 is a key prognostic marker and therapeutic target in aggressive and proliferative hepatoblastoma.Molecular cancer · 2026Article
- Upregulation of the lncRNACells · 2026Article
- Integrative bioinformatics analysis identifies ubiquitin-related genes and their regulatory networks in hepatoblastoma.Discover oncology · 2026Article
- Epigenetic reprogramming of hepatic antigen presenting cells in chronic liver disease.Frontiers in immunology · 2026Review
- Noncoding RNAs: A Novel Frontier in Liver Cancer Research and Therapy: Implications for Precision Oncology.Sub-cellular biochemistry · 2026Review
- Review
- Single-cell profiles delineate immune cell remodeling and enhanced tumor-fibroblast interaction of hepatoblastoma after chemotherapy.Cell reports. Medicine · 2025Article
- Derivation of Genetically Defined Murine Hepatoblastoma Cell Lines with Angiogenic Potential.Cancers · 2025Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
57 authors at 20 institutions in 10 countries.
Funding
Abstract
BACKGROUND &
aimsHepatoblastoma (HB) is a rare disease. Nevertheless, it is the predominant pediatric liver cancer, with limited therapeutic options for patients with aggressive tumors. Herein, we aimed to uncover the mechanisms of HB pathobiology and to identify new biomarkers and therapeutic targets in a move towards precision medicine for patients with advanced HB.
methodsWe performed a comprehensive genomic, transcriptomic and epigenomic characterization of 159 clinically annotated samples from 113 patients with HB, using high-throughput technologies.
resultsWe discovered a widespread epigenetic footprint of HB that includes hyperediting of the tumor suppressor BLCAP concomitant with a genome-wide dysregulation of RNA editing and the overexpression of mainly non-coding genes of the oncogenic 14q32 DLK1-DIO3 locus. By unsupervised analysis, we identified 2 epigenomic clusters (Epi-CA, Epi-CB) with distinct degrees of DNA hypomethylation and CpG island hypermethylation that are associated with the C1/C2/C2B transcriptomic subtypes. Based on these findings, we defined the first molecular risk stratification of HB (MRS-HB), which encompasses 3 main prognostic categories and improves the current clinical risk stratification approach. The MRS-3 category (28%), defined by strong 14q32 locus expression and Epi-CB methylation features, was characterized by CTNNB1 and NFE2L2 mutations, a progenitor-like phenotype and clinical aggressiveness. Finally, we identified choline kinase alpha as a promising therapeutic target for intermediate and high-risk HBs, as its inhibition in HB cell lines and patient-derived xenografts strongly abrogated tumor growth.
conclusionsThese findings provide a detailed insight into the molecular features of HB and could be used to improve current clinical stratification approaches and to develop treatments for patients with HB. LAY SUMMARY: Hepatoblastoma is a rare childhood liver cancer that has been understudied. We have used cutting-edge technologies to expand our molecular knowledge of this cancer. Our biological findings can be used to improve clinical management and pave the way for the development of novel therapies for this cancer.
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