In:
Nature Communications, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2018-08-08)
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.
Type of Medium:
Online Resource
ISSN:
2041-1723
DOI:
10.1038/s41467-018-05550-5
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2018
detail.hit.zdb_id:
2553671-0
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