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Cited by 221Epigenetics and DNA MethylationCancer-related molecular mechanisms researchCancer-related gene regulation

Hypermethylation of gene body CpG islands predicts high dosage of functional oncogenes in liver cancer

Open access
Arechederra, Maria, Daian, Fabrice, Yim, Annie, Bazai, Sehrish K., Richelme, Sylvie, Dono, Rosanna, Saurin, Andrew J., Habermann, Bianca H. +1 more·2018·Nature Communications
DOI 10.1038/s41467-018-05550-5PMC PMC6082886
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Abstract

Epigenetic modifications such as aberrant DNA methylation reshape the gene expression repertoire in cancer. Here, we used a clinically relevant hepatocellular carcinoma (HCC) mouse model ( Alb-R26 Met ) to explore the impact of DNA methylation on transcriptional switches associated with tumorigenesis. We identified a striking enrichment in genes simultaneously hypermethylated in CpG islands (CGIs) and overexpressed. These hypermethylated CGIs are located either in the 5′-UTR or in the gene body region. Remarkably, such CGI hypermethylation accompanied by gene upregulation also occurs in 56% of HCC patients, which belong to the “HCC proliferative-progenitor” subclass. Most of the genes upregulated and with hypermethylated CGIs in the Alb-R26 Met HCC model undergo the same change in a large proportion of HCC patients. Among reprogrammed genes, several are well-known oncogenes. For others not previously linked to cancer, we demonstrate here their action together as an “oncogene module”. Thus, hypermethylation of gene body CGIs is predictive of elevated oncogene levels in cancer, offering a novel stratification strategy and perspectives to normalise cancer gene dosages.

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Authors
Arechederra, M., Daian, F., Yim, A., Bazai, S. K., Richelme, S., Dono, R., Saurin, A. J., Habermann, B. H., & Maina, F.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Max Planck Institute of Biochemistry (DE)
Corresponding author
Maina, Flavio
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2018-08-08
Volume
9
Issue
1
Pages
3164-3164
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-018-05550-5
PMC
PMC6082886
OpenAlex
W2887200576
Cited by
221
References
53
Citations by year
2026: 4 · 2025: 20 · 2024: 23 · 2023: 23 · 2022: 45 · 2021: 55 · 2020: 29 · 2019: 18 · 2018: 2 · 2017: 1
FWCI
9.25
Type
journal article
Language
en
Update notices
correction (2018-09-25)
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • HAL AMU (submittedVersion, other-oa)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Max Planck Digital Library (submittedVersion, other-oa)
  • MPG.PuRe (Max Planck Society) (submittedVersion, cc-by)
Funders
  • Aix-Marseille Université
  • Deutsche Forschungsgemeinschaft (HA 6905/2-1)
  • Fondation de France
  • Institut National Du Cancer
  • Groupement des Entreprises Françaises dans la lutte contre le Cancer
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
Keywords
DNA hypermethylation, hepatocellular carcinoma, gene expression reprogramming, cancer stratification, epigenetic reprogramming, carcinogenesis
MeSH terms
Animals, Disease Models, Animal, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Mice, Inbred C57BL, Mice, Transgenic, Oncogenes, Promoter Regions, Genetic, Up-Regulation, Gene Expression Regulation, Neoplastic, Gene Dosage, CpG Islands, DNA Methylation, Epigenesis, Genetic, Cell Line, Tumor, Mice, Carcinogenesis

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