Hypermethylation of gene body CpG islands predicts high dosage of functional oncogenes in liver cancer.
Nat Commun
; 9(1): 3164, 2018 08 08.
Article
en En
| MEDLINE
| ID: mdl-30089774
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. 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oncogenes
/
Regulación Neoplásica de la Expresión Génica
/
Dosificación de Gen
/
Islas de CpG
/
Metilación de ADN
/
Neoplasias Hepáticas
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Francia