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

Author

Listed:
  • Maria Arechederra

    (Aix Marseille Univ)

  • Fabrice Daian

    (Aix Marseille Univ)

  • Annie Yim

    (Max Planck Institute of Biochemistry)

  • Sehrish K. Bazai

    (Aix Marseille Univ)

  • Sylvie Richelme

    (Aix Marseille Univ)

  • Rosanna Dono

    (Aix Marseille Univ)

  • Andrew J. Saurin

    (Aix Marseille Univ)

  • Bianca H. Habermann

    (Aix Marseille Univ)

  • Flavio Maina

    (Aix Marseille Univ)

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-R26Met) 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-R26Met 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.

Suggested Citation

  • Maria Arechederra & Fabrice Daian & Annie Yim & Sehrish K. Bazai & Sylvie Richelme & Rosanna Dono & Andrew J. Saurin & Bianca H. Habermann & Flavio Maina, 2018. "Hypermethylation of gene body CpG islands predicts high dosage of functional oncogenes in liver cancer," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05550-5
    DOI: 10.1038/s41467-018-05550-5
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    Cited by:

    1. Danni A. Gadd & Robert F. Hillary & Daniel L. McCartney & Liu Shi & Aleks Stolicyn & Neil A. Robertson & Rosie M. Walker & Robert I. McGeachan & Archie Campbell & Shen Xueyi & Miruna C. Barbu & Claire, 2022. "Integrated methylome and phenome study of the circulating proteome reveals markers pertinent to brain health," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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