Gallon, John; Coto-Llerena, Mairene; Ercan, Caner; Bianco, Gaia; Paradiso, Viola; Nuciforo, Sandro; Taha-Melitz, Stephanie; Meier, Marie-Anne; Boldanova, Tujana; Pérez-Del-Pulgar, Sofía; Rodríguez-Tajes, Sergio; von Flüe, Markus; Soysal, Savas D; Kollmar, Otto; Llovet, Josep M; Villanueva, Augusto; Terracciano, Luigi M; Heim, Markus H; Ng, Charlotte K. Y. and Piscuoglio, Salvatore (2022). Epigenetic priming in chronic liver disease impacts the transcriptional and genetic landscapes of hepatocellular carcinoma. Molecular oncology, 16(3), pp. 665-682. Wiley 10.1002/1878-0261.13154
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Molecular_Oncology_-_2021_-_Gallon_-_Epigenetic_priming_in_chronic_liver_disease_impacts_the_transcriptional_and_genetic.pdf - Accepted Version Available under License Creative Commons: Attribution (CC-BY). Download (18MB) | Preview |
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Molecular_Oncology_-_2021_-_Gallon_-_Epigenetic_priming_in_chronic_liver_disease_impacts_the_transcriptional_and_genetic.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (3MB) | Preview |
Hepatocellular carcinomas (HCCs) usually arise from chronic liver disease (CLD). Pre-cancerous cells in chronically inflamed environments may be 'epigenetically primed', sensitising them to oncogenic transformation. We investigated whether epigenetic priming in CLD may affect HCC outcomes by influencing the genomic and transcriptomic landscapes of HCC. Analysis of DNA methylation arrays in ten paired CLD-HCC identified 339 shared dysregulated CpG sites and 18 shared differentially methylated regions compared to healthy livers. These regions were associated with dysregulated expression of genes with relevance in HCC, including Ubiquitin D (UBD), Cytochrome P450 Family 2 Subfamily C Member 19 (CYP2C19) and O-6-Methylguanine-DNA Methyltransferase (MGMT). Methylation changes were recapitulated in an independent cohort of nine paired CLD-HCC. High CLD methylation score, defined using the 124 dysregulated CpGs in CLD and HCC in both cohorts, was associated with poor survival, increased somatic genetic alterations, and TP53 mutations in two independent HCC cohorts. Oncogenic transcriptional and methylation dysregulation is evident in CLD and compounded in HCC. Epigenetic priming in CLD sculpts the transcriptional landscape of HCC and creates an environment favouring the acquisition of genetic alterations, suggesting that the extent of epigenetic priming in CLD could influence disease outcome.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) |
UniBE Contributor: |
Ng, Kiu Yan Charlotte |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1878-0261 |
Publisher: |
Wiley |
Language: |
English |
Submitter: |
Rahel Fuhrer |
Date Deposited: |
12 Jan 2022 14:22 |
Last Modified: |
05 Dec 2022 15:56 |
Publisher DOI: |
10.1002/1878-0261.13154 |
PubMed ID: |
34863035 |
Uncontrolled Keywords: |
Chronic liver disease epigenetic priming hepatocellular carcinoma methylation |
BORIS DOI: |
10.48350/162331 |
URI: |
https://boris.unibe.ch/id/eprint/162331 |
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