Aberrant DNA methylation of imprinted loci in hepatocellular carcinoma and after in vitro exposure to common risk factors

Clinical Epigenetics
Marie-Pierre LambertZdenko Herceg

Abstract

Hepatocellular carcinoma (HCC) is among the most frequent human malignancies and a major cause of cancer-related death worldwide. It is characterized by late detection and fast progression, and it is believed that epigenetic disruption may be one of the molecular mechanisms leading to hepatocarcinogenesis. Previous studies from our group revealed that HCC tumors exhibit specific DNA methylation signatures associated with major risk factors and tumor progression. Imprinted genes are mono-allelically expressed in a parent-of-origin-dependent manner and have been suggested to be more susceptible to deregulation in cancer. To test this notion, we performed a targeted analysis of DNA methylation in known imprinted genes, using HCC samples and in vitro models of carcinogenic exposure. Analysis of HCC DNA methylation in two independent datasets showed that differentially methylated loci are significantly enriched in imprinted genes. Most of the promoters of imprinted genes were found hypomethylated in HCC tumors compared to surrounding tissues, contrasting with the frequent promoter hypermethylation observed in tumors. We next investigated the status of methylation of the imprinting control region (ICR) of different imprinted clusters...Continue Reading

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Citations

Aug 27, 2018·Journal of Leukocyte Biology·Mélanie KirchmeyerIris Behrmann
Nov 14, 2015·Oncotarget·Pierre-Benoit AnceyHector Hernandez-Vargas
Apr 13, 2017·BioMed Research International·Braira WahidMuhammad Idrees
Jul 14, 2018·Scientific Reports·Yoon ChoJae-Chun Ryu
Apr 19, 2016·Epigenetics : Official Journal of the DNA Methylation Society·Guillermo A Silva-MartínezGertrud Lund
May 21, 2020·Cancers·Lysann Tietze, Sonja M Kessler
May 1, 2021·Journal of Clinical Medicine·Mirjam B ZeiselMassimo Levrero

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Methods Mentioned

BETA
methylation profiling
PCR
dot blot
Assay

Software Mentioned

MethHC
BRBArrayTools
NIS
Elements
R
Bioconductor
TCGA

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